Bicyclic heterocyclic derivatives as bromodomain inhibitors

ABSTRACT

The present disclosure provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R 1 , R 2 , R 3 , R 4 , L 1 , L 2 , Cy 1 , Cy 2 , X, n, and dotted line have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders associated as bromodomain inhibitors. The present disclosure also provides preparation of compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent, or excipient.

This is a national stage application under § 371 of International PatentApplication No. PCT/IB2015/050090, filed Jan. 6, 2015, which claims thebenefit of Indian provisional application number 125/CHE/2014 filed on 9Jan. 2014, both of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to bicyclic heterocyclic derivatives offormula (I) which are useful as bromodomain inhibitors.

The invention also relates to process for preparation thereof,pharmaceutical compositions comprising them, and their use for treatmentand prevention in diseases or disorder, in particular their use intreatment of diseases or disorder associated with bromodomaininhibition.

BACKGROUND OF THE INVENTION

The acetylation of histone lysine is central to providing the dynamicregulation of chromatin-based gene transcription. The bromodomain (BRD),which is the conserved structural module in chromatin-associatedproteins and histone acetyltransferases, is the sole protein domainknown to recognize acetyl-lysine residues on proteins.

The BET family of bromodomain containing proteins comprises 4 proteins(BRD2, BRD3, BRD4 and BRD-t) which contain tandem bromodomains capableof binding to two acetylated lysine residues in close proximity,increasing the specificity of the interaction. BRD2 and BRD3 arereported to associate with histones along actively transcribed genes andmay be involved in facilitating transcriptional elongation (Leroy et al,Mol. Cell. 2008 30(1):51-60), while BRD4 appears to be involved in therecruitment of the pTEF-[beta] complex to inducible genes, resulting inphosphorylation of RNA polymerase and increased transcriptional output(Hargreaves et al, Cell, 2009 138(1): 129-145). It has also beenreported that BRD4 or BRD3 may fuse with NUT (nuclear protein in testis)forming novel fusion oncogenes, BRD4-NUT or BRD3-NUT, in a highlymalignant form of epithelial neoplasia (French et al. Cancer Research,2003, 63, 304-307 and French et al. Journal of Clinical Oncology, 2004,22 (20), 4135-4139). Data suggests that BRD-NUT fusion proteinscontribute to carcinogenesis (Oncogene, 2008, 27, 2237-2242). BRD-t isuniquely expressed in the testes and ovary. All family members have beenreported to have some function in controlling or executing aspects ofthe cell cycle, and have been shown to remain in complex withchromosomes during cell division suggesting a role in the maintenance ofepigenetic memory. In addition some viruses make use of these proteinsto tether their genomes to the host cell chromatin, as part of theprocess of viral replication (You et al Cell, 2004 117(3):349-60).

Japanese patent application JP2008156311 discloses a benzimidazolederivative which is said to be a BRD2 bromodomain binding agent hasutility with respect to virus infection/proliferation.

International patent application WO2009084693A1 discloses a series ofthienotriazolodiazepiene derivatives that are said to inhibit thebinding between an acetylated histone and a bromodomain containingprotein which are said to be useful as anti-cancer agents.

International patent application WO2011054846A1 discloses a series ofquinoline derivatives that inhibit the binding of BET familybromodomains with acetylated lysine residues.

However, there remains a need for potent bromodomain inhibitors withdesirable pharmaceutical properties. Certain bicyclic heterocyclicderivatives have been found in the context of this invention to have aclass of compounds that inhibit the binding of BET family bromodomainsto acetylated lysine residues for controlling the gene expressions inhuman health and disease. Such compounds will hereafter be referred toas “bromodomain inhibitors”.

SUMMARY OF THE INVENTION

The present invention provides bicyclic heterocyclic derivatives of theformula (I) that inhibit the binding of BET family bromodomains toacetylated lysine residues.

or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof;wherein,

dotted line[---] represents a single or a double bond;

X is selected from C, C(O), N or O; wherein C and N are substituted withone or more R₅ to meet the desired valency requirements;

L₁ is a direct bond or a linker selected from —NH—, —NHC(O)— or—NHS(O)₂—;

L₂ is a linker selected from —(CHR₆)_(n)—, —C(O)— or —S(O)₂—;

Cy₁ is an optionally substituted 5-6 membered monocyclic ring containing1-4 hetero atoms/hetero groups independently selected form N, NH, O or—C(O)—; wherein the optional substituent at each occurrence isindependently selected from one or more R₇;

Cy₂ is an optionally substituted 4-12 membered monocyclic or bicyclicring containing 0-3 hetero atoms/groups independently selected form N,NH, O or S; wherein the optional substituent at each occurrence isindependently selected from one or more R₈;

R₁ is selected from hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, aminoalkyl, heterocyclyl or heterocyclylalkyl;

R₂ and R₃ independently are hydrogen, alkyl or together form an oxogroup;

R₄ at each occurrence is independently selected from hydrogen, alkyl,cycloalkyl, cyanoalkyl, hydroxyalkyl, or optionally substitutedhaloalkyl; wherein the optional substituent is one or more hydroxyl;

R₅ at each occurrence is independently selected from hydrogen, alkyl,haloalkyl, cycloalkyl or cyano;

R₆ is hydrogen or alkyl;

R₇ is selected from alkyl, hydroxy or cycloalkyl;

R₈ is selected from alkyl, alkoxy, amino, cyano, halogen, haloalkyl,hydroxy, —C(O)alkyl or optionally substituted heterocyclyl; wherein theoptional substituent is selected from one or more alkyl or hydroxy; and

n is an integer selected from 1 or 2.

In one aspect of the present invention, it relates to pharmaceuticalcomposition comprising bicyclic heterocyclic derivatives of formula (I)and processes for preparing thereof.

In yet another aspect of the present invention, it provides use ofbicyclic heterocyclic derivatives of formula (I) for the treatment andprevention in diseases or disorder, in particular their use in diseasesor disorder for which a bromodomain inhibitor is indicated.

In further yet another aspect, the invention relates to use of novelbicyclic heterocyclic derivatives of formula (I) or a pharmaceuticallyacceptable salt or a pharmaceutically acceptable stereoisomer thereof,including mixtures thereof in all ratios as a medicament for which abromodomain inhibitor is indicated.

DETAILED DESCRIPTION OF THE INVENTION

An embodiment of the present invention provides bicyclic heterocyclicderivatives of formula (I) useful as bromodomain inhibitors.

One of the embodiments of the present invention relates to compounds offormula (I):

or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof;wherein,

dotted line[---] represents a single or a double bond;

X is selected from C, C(O), N or O; wherein C and N are substituted withone or more R₅ to meet the desired valency requirements;

L₁ is a direct bond or a linker selected from —NH—, —NHC(O)— or—NHS(O)₂—;

L₂ is a linker selected from —(CHR₆)_(n)—, —C(O)— or —S(O)₂—;

Cy₁ is an optionally substituted 5-6 membered monocyclic ring containing1-4 hetero atoms/hetero groups independently selected form N, NH, O or—C(O)—; wherein the optional substituent at each occurrence isindependently selected from one or more R₇;

Cy₂ is an optionally substituted 4-12 membered monocyclic or bicyclicring containing 0-3 hetero atoms/groups independently selected form N,NH, O or S; wherein the optional substituent at each occurrence isindependently selected from one or more R₈;

R₁ is selected from hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, aminoalkyl, heterocyclyl or heterocyclylalkyl;

R₂ and R₃ independently are hydrogen, alkyl or together form an oxogroup;

R₄ at each occurrence is independently selected from hydrogen, alkyl,cycloalkyl, cyanoalkyl, hydroxyalkyl, or optionally substitutedhaloalkyl; wherein the optional substituent is one or more hydroxyl;

R₅ at each occurrence is independently selected from hydrogen, alkyl,haloalkyl, cycloalkyl or cyano;

R₆ is hydrogen or alkyl;

R₇ is selected from alkyl, hydroxy or cycloalkyl;

R₈ is selected from alkyl, alkoxy, amino, cyano, halogen, haloalkyl,hydroxy, —C(O)alkyl or optionally substituted heterocyclyl; wherein theoptional substituent is selected from one or more alkyl or hydroxy; and

n is an integer selected from 1 or 2.

The embodiments below are illustrative of the present invention and arenot intended to limit the claims to the specific embodimentsexemplified.

According to one embodiment, specifically provided are compounds of theformula (I), in which X is selected from O, N, C(O), CH₂, CH, C(R₅)₂ orCR₅.

According to above embodiment, R₅ is selected from alkyl, haloalkyl,cycloalkyl or cyano; in particular alkyl is methyl, haloalkyl is —CF₃and cycloalkyl is cyclopropyl.

According to other embodiment, specifically provided are compounds ofthe formula (I), in which L₁ is a direct bond.

According to yet another embodiment, specifically provided are compoundsof the formula (I), in which L₁ is a linker selected from —NH—, —NHC(O)—or —NHS(O)₂—.

According to further yet another embodiment, specifically provided arecompounds of the formula (I), in which Cy₁ is selected from optionallysubstituted 5- or 6-membered monocyclic ring containing 1-3 heteroatoms/hetero groups independently selected form N, NH, O or —C(O)—.

According to preceding embodiment, Cy₁ is selected from the groupconsisting of

According to further yet another embodiment, specifically provided arecompounds of formula (I), in which L₂ is selected from —(CHR₆)_(n)—,—C(O)— or —S(O)₂—; in which ‘n’ is an integer selected from 1 or 2 andR₆ is selected from hydrogen or alkyl; in particular alkyl is methyl.

According to further yet another embodiment, specifically provided arecompounds of the formula (I), in which Cy₂ is selected from optionallysubstituted 5- or 6-membered monocyclic ring or 12 membered bicyclicring containing 0-3 hetero atoms/groups independently selected from N,N(H), O or S.

According to preceding embodiment, Cy₂ is selected from the groupconsisting of thiazole, pyrazine, tetrahydro-2H-pyran, morpholine,pyrimidine, quinoline, optionally substituted piperidine, optionallysubstituted phenyl or optionally substituted pyridyl.

According to preceding embodiments, optional substituents are selectedfrom halogen, alkoxy, amino, cyano, alkyl, haloalkyl, hydroxy,—C(O)alkyl and heterocyclyl; in particular alkyl is methyl, halogen isfluoro, chloro or bromo, alkoxy is methoxy, —C(O)alkyl is propan-1-one,and heterocyclyl is pyrrolidin-3-ol, 3,5-dimethyl-1H-pyrazole and1-methyl-1H-pyrazole.

According to further yet another embodiment, specifically provided arecompounds of the formula (I), in which R₁ is hydrogen, alkyl, alkenyl,haloalkyl, hydroxyalkyl, alkoxyalkyl or alkyl substituted aminoalkyl; inparticular alkyl is methyl or butyl, alkenyl is prop-1-ene, hydroxyalkylis —(CH₂)₂OH or —(CH₂)₃OH, haloalkyl is —CF₃ or —CH₂CF₃, alkoxyalkyl ismethoxyethyl, and aminoalkyl is dimethylaminoethyl.

According to further yet another embodiment, specifically provided arecompounds of the formula (I), in which R₁ is heterocyclyl orheterocyclylalkyl; in particular heterocyclyl is piperidine, andheterocyclylalkyl is morpholinyl-ethyl, piperdinyl-methyl,piperdinyl-ethyl, piperazinyl-ethyl, pyridyl-methyl,tetrahydropyran-methyl and pyrrolidinyl-ethyl.

According to further yet another embodiment, specifically provided arecompounds of the formula (I), in which R₄ is hydrogen, alkyl,cycloalkyl, cyanoalkyl, hydroxyalkyl or optionally substitutedhaloalkyl; in particular alkyl is methyl, cycloalkyl is cyclohexyl,cyanoalkyl is —CH₂CN, hydroxyalkyl is —CH₂OH; and optionally substitutedhaloalkyl is —CH₂F, —CH(OH)CF₃ or —C(OH)(OH)CF₃.

According to yet another embodiment of the present invention, thecompound of formula (I) is a compound of formula (Ia):

wherein,R₁, R₂, R₃, R₄, Cy₁, Cy₂, L₁, L₂ and ‘n’ are same as defined in formula(I);or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof.

According to yet another embodiment of the present invention, thecompound of formula (I) is a compound of formula (Ib):

wherein,R₁, R₂, R₃, R₄, Cy₁, Cy₂, L₁, L₂ and ‘n’ are same as defined in formula(I);or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof.

According to yet another embodiment of the present invention, thecompound of formula (I) is a compound of formula (Ic):

wherein,R₁, R₂, R₃, R₄, Cy₁, Cy₂, L₁, L₂ and ‘n’ are same as defined in formula(I);or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof.

In yet another particular embodiment of the present invention, thecompound of formula (I) is selected from the group consisting of:

Compound. No IUPAC Name  1.4-(4-chlorobenzyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine;  2.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-methoxypyridin-2-yl)methyl)quinolin-2(1H)-one;  3.6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;  4.1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinoxalin-2(1H)-one;  5. 1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one;  6.4-(1-(4-chlorophenyl)ethyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine;  7.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-3-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine;  8.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrazin-2-ylmethyl)quinolin-2(1H)-one;  9.6-(3,5-dimethylisoxazol-4-yl)-1-((3-fluoropyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one; 10.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one; 11.4-((3-chlorophenyl)sulfonyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine; 12.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(pyridin-3-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine; 13.N-(4-(4-chlorobenzyl)-6-methoxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3,5-dimethylisoxazole-4-sulfonamide; 14.1-((4-chlorophenyl)sulfonyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 15.1-(4-chlorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 16.2-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)aniline; 17.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 18.4-(4-chlorobenzyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 19.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-4-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-1); 20.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-4-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-2); 21.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(pyridin-3-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 22.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(pyridin-2-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 23.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((tetrahydro-2H-pyran-4-yl)methyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 24.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-3-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-1); 25.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-3-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-2); 26.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((6-methoxypyridin-3-yl)methyl)- 2H-benzo[b][1,4]oxazin-3(4H)-one; 27.6-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)nicotinonitrile; 28.4-((5-chloropyridin-2-yl)methyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 29.7-(3,5-dimethylisoxazol-4-yl)-4-((5-fluoropyridin-2-yl)methyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 30.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((5-methoxypyridin-2-yl)methyl)- 2H-benzo[b][1,4]oxazin-3(4H)-one; 31.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(1-(pyridin-2-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 32.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((6-methylpyridin-3-yl)methyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 33.4-(1-(4-chlorophenyl)ethyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-1); 34.4-(1-(4-chlorophenyl)ethyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one (Isomer-2); 35.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(2-(pyridin-2-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 36.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2(1H)-one; 37.1-((5-chloropyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 38.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(2-morpholinoethyl)quinolin-2(1H)-one; 39.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(thiazol-2-ylmethyl)quinolin-2(1H)-one; 40.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(1-(pyridin-2-yl)ethyl)quinolin-2(1H)-one; 41.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(1-(pyridin-3-yl)ethyl)quinolin-2(1H)-one; 42.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-one; 43.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrimidin-2-ylmethyl)quinolin-2(1H)-one; 44.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrimidin-4-ylmethyl)quinolin-2(1H)-one; 45.6-(3,5-dimethylisoxazol-4-yl)-1-((5-fluoropyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one; 46.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 47.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(trifluoromethyl)pyridin-2-yl)methyl)quinolin-2(1H)-one; 48.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-4,4-dimethyl-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one; 49.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2,2-dimethyl-4-(pyridin-3-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 50.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 51.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridin-2-ylmethyl)quinoline-2,4(1H,3H)-dione; 52.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one; 53.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-4-methyl-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 54.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-4-(trifluoromethyl)quinolin-2(1H)-one; 55.4-cyclopropyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 56.1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;57.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(quinolin-2-ylmethyl)quinolin-2(1H)-one; 58.1-((5-chloropyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methylquinolin-2(1H)-one; 59.1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methylquinolin-2(1H)-one; 60.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(piperidin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 61.6-(6-hydroxypyridin-3-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;62. 6-(3-cyclopropyl-5-methylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 63.7-methoxy-6-(5-methylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;64.7-methoxy-6-(3-methylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;65. 4-(4-chlorobenzyl)-7-(3,5-dimethyl-1H-pyrazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 66.6-(3,5-dimethyl-1H-pyrazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 67.1-((6-chloropyridin-3-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 68.3-cyclohexyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 69.3-cyclohexyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2(1H)-one; 70.7-(3,5-dimethylisoxazol-4-yl)-4-((6-hydroxypyridin-3-yl)methyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 71.7-(3,5-dimethylisoxazol-4-yl)-6-(2-methoxyethoxy)-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 72.6-(3,5-dimethylisoxazol-4-yl)-7-hydroxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 73.1-((5-chloropyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-hydroxyquinolin-2(1H)-one; 74.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2,2,2-trifluoroethoxy)quinolin-2(1H)-one; 75.6-(3,5-dimethylisoxazol-4-yl)-7-(2-morpholinoethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 76.7-(2-(dimethylamino)ethoxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 77.6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 78.7-butoxy-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 79.7-(allyloxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 80.6-(3,5-dimethylisoxazol-4-yl)-7-(2-hydroxyethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 81.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinolin-2(1H)-one; 82.6-(3,5-dimethylisoxazol-4-yl)-7-(2-(piperazin-1-yl)ethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 83.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(pyridin-4-ylmethoxy)quinolin-2(1H)-one; 84.6-(3,5-dimethylisoxazol-4-yl)-7-(3-hydroxypropoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 85.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(trifluoromethoxy)quinolin-2(1H)-one; 86.6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-yloxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 87.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-((tetrahydro-2H-pyran-4-yl)methoxy)quinolin-2(1H)-one; 88.6-(3,5-dimethylisoxazol-4-yl)-7-(2-(piperidin-4-yl)ethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 89.6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2-(pyrrolidin-3-yl)ethoxy)quinolin-2(1H)-one hydrochloride; 90.7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((1-propionylpiperidin-4-yl)methyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 91.7-methoxy-6-(5-methyl-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 92.3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione; 93.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinoxalin-2(1H)-one; 94.N-(4-(4-chlorobenzyl)-6-methoxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3,5-dimethylisoxazole-4-carboxamide; 95.4-(4-chlorobenzyl)-7-((3,5-dimethylisoxazol-4-yl)amino)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one; 96.6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 97.6-(3,5-dimethylisoxazol-4-yl)-3-(fluoromethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one; 98.6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)quinolin-2(1H)-one;  98a1-((5-bromopyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 99.1-((5-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one; 100. 6-(3,5-dimethylisoxazol-4-yl)-1-((5-(3-hydroxypyrrolidin-1-yl)pyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one; 101. 6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2- trifluoro-1-hydroxyethyl)quinolin-2(1H)-one; 102. 6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2- trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(Isomer-1); 103. 6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2- trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(Isomer-2); 104. 6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2- trifluoro-1,1-dihydroxyethyl)quinolin-2(1H)-one; 105. 1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-2-oxo-1,2-dihydroquinoline-4-carbonitrile; and 106. 2-(1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)acetonitrile,or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof.

In a further embodiment, the present invention provides processes forpreparing novel bicyclic heterocyclic derivatives of formula (I).

It should be understood that the compounds of formula (I), (Ia), (Ib)and (Ic) structurally encompasses all stereoisomers, enantiomers anddiastereomers, and pharmaceutically acceptable salts that may becontemplated from the chemical structure of the general formula (I)described herein.

The absolute configuration at an asymmetric atom is specified by eitherR or S. Resolved compounds whose absolute configuration is not known canbe designated by (+) or (−) depending on the direction in which theyrotate plane polarized light. When a specific stereoisomer isidentified, this means that said stereoisomer is substantially free,i.e. associated with less than 50%, preferably less than 20%, morepreferably less than 5%, in particularly less than 2% or 1% of the otherisomers. Thus when a compound of formula (1) is for instance specifiedas (R), this means that the compound is substantially free of (S)isomer; when the compound of formula (1) is for instance specified as E,this means that the compound is free of the Z isomer; when the compoundof formula (1) is for instance specified as cis isomer, this means thatthe compound is free of the trans isomer.

In yet another embodiment according to the present invention, itprovides a pharmaceutical composition comprising the compound of formula(I) of the present invention and at least one pharmaceuticallyacceptable excipient (such as a pharmaceutically acceptable carrier ordiluent). Preferably, the pharmaceutical composition comprises atherapeutically effective amount of at least one compound describedherein.

In yet another embodiment of the present invention relates to thepharmaceutical combination comprising the compound of formula (I) of thepresent invention and at least one additional pharmaceuticallyacceptable therapeutic agent. Preferably, the additionalpharmaceutically acceptable therapeutic agent can be anticancer agent,autoimmune agent, cardiovascular agents and/or inflammatory agents.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in artto which the subject matter herein belongs. As used herein, thefollowing definitions are supplied in order to facilitate theunderstanding of the present invention.

“Alkyl” refers to a hydrocarbon chain that may be a straight chain orbranched chain, containing the indicated number of carbon atoms, forexample, a C₁-C₆ alkyl group may have from 1 to 6 (inclusive) carbonatoms in it. Examples of C₁-C₆ alkyl groups include, but are not limitedto, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl,sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

“Alkenyl” refers to a hydrocarbon chain that may be a straight chain orbranched chain, containing the indicated number of carbon atoms havingat least one —C═C—, for example, a C₂-C₆ alkenyl group may have from 2to 6 (inclusive) —C═C— atoms in it. Examples of C₂-C₆ alkenyl groupsinclude, but are not limited to ethylene, prop-1-ene, but-1-ene,but-2-ene, pent-1-ene, pent-2-ene, hex-1-ene, hex-2-ene and the like.

“Alkoxy” refers to the group Ak-O— or —O-Ak, where Ak is an alkyl group,as defined above. Exemplary C₁-C₆ alkyl group containing alkoxy groupsinclude but are not limited to methoxy, ethoxy, n-propoxy, 1-propoxy,isopropoxy, n-butoxy and t-butoxy.

“Alkoxyalkyl” refers to an alkyl group substituted with one or morealkoxy groups; the alkyl group and alkoxy groups are same as definedabove. Representative examples of an alkoxyalkyl group include but arenot limited to —CH₂OCH₃, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CH₂CH₂OCH₂CH₃ andthe like.

“Cyanoalkyl” refers to an alkyl group, as defined above, wherein one ormore of the alkyl group's hydrogen atoms have been replaced with —CN.Representative examples of an cyanoalkyl group include, but are notlimited to —CH₂CN, —CH₂CH₂CN, —C(CH₂)₂CN, —CH₂CH₂CH₂CN and the like.

“Aryl” refers to an optionally substituted monocyclic, bicyclic orpolycyclic aromatic hydrocarbon ring system of about 6 to 14 carbonatoms. Examples of a C₆-C₁₄aryl group include, but are not limited tophenyl, naphthyl, biphenyl, anthryl, biphenylenyl, and acenaphthyl.

“Cycloalkyl” refers to a C₃-C₁₀ non-aromatic, saturated, monocyclic,bicyclic or polycyclic hydrocarbon ring system. Representative examplesof a C₃-C₁₀ cycloalkyl include, but are not limited to, cyclopropyl,cyclopentyl, cyclohexyl, cyclooctyl and the like.

“Cyano” refers to —CN group.

“Hydroxy” refers to —OH group.

“Amino” refers to an —NH₂ group.

“Aminoalkyl” refers to an alkyl group, as defined above, wherein one ormore of the alkyl group's hydrogen atom has been replaced with aminogroup. Moreover one or more hydrogen atoms on the amino group can bereplaced by one or more alkyl group. Representative examples of aaminoalkyl group include, but are not limited to —CH₂NH₂, —CH₂N(H)CH₃,—CH₂N(CH₃)₂, —(CH₂)₂NH₂, —(CH₂)₂N(H)CH₃, —(CH₂)₂N(CH₃)₂ and the like.

“Hydroxyalkyl” refers to an alkyl group, as defined above, wherein oneor more of the alkyl group's hydrogen atom has been replaced with —OHgroup. Representative examples of a hydroxylalkyl group include, but arenot limited to methanol, ethanol, propanol, isopropanol, butanol,butan-2-ol and hexanol.

“Halo” or “halogen” refers to —F, —Cl, —Br and —I.

“Haloalkyl” refers to an alkyl group, as defined above, wherein one ormore of the alkyl group's hydrogen atoms has been replaced with —F, —Cl,—Br or —I. Representative examples of an haloalkyl group include, butare not limited to —CH₂F, —CCl₃, —CF₃, —CH₂Cl, —CH₂CH₂Br, —CH₂CH₂I,—CH₂CH₂CH₂F, —CH₂CH₂CH₂Cl, —CH₂CH₂CH₂CH₂Br, —CH₂CH₂CH₂CH₂I,—CH₂CH₂CH₂CH₂CH₂Br, —CH₂CH₂CH₂CH₂CH₂I, —CH₂CH(Br)CH₃, —CH₂CH(Cl)CH₂CH₃,and —CH(F)CH₂CH₃.

The term “Heterocyclyl” includes the definitions of “heterocycloalkyl”and “heteroaryl”.

The term “Heterocycloalkyl” refers to a non-aromatic, saturated,monocyclic ring system of 5 to 10 member having at least one heteroatomor heterogroup selected from O, N, S, S(O), S(O)₂, NH and C(O).Exemplary heterocycloalkyl groups include piperdinyl, piperazinyl,pyrrolidinyl, morpholinyl, thiomorpholinyl, 1,3-dioxolanyl,1,4-dioxanyl,tetrahydro-2H-pyran and the like.

“Heteroaryl” refers to an unsaturated, monocyclic, bicyclic, orpolycyclic aromatic ring system containing at least one heteroatomselected from oxygen, sulfur and nitrogen. Examples of C₅-C₁₂ heteroarylgroups include furan, thiophene, indole, azaindole, oxazole, thiazole,thiadiazole, isoxazole, isothiazole, imidazole, imidazol-2-one,N-methylimidazole, pyridine, pyrimidine, pyrazine, pyrrole,pyrrole-2,5-dione, N-methylpyrrole, pyrazole, N-methylpyrazole,1,3,4-oxadiazole, 1,2,4-triazole, 1-methyl-1,2,4-triazole, 1H-tetrazole,1-methyltetrazole, benzoxazole, benzothiazole, benzofuran,benzisoxazole, benzimidazole, N-methylbenzimidazole, azabenzimidazole,indazole, quinazoline, quinoline and isoquinoline. Bicyclic heteroarylgroups include those where a phenyl, pyridine, pyrimidine or pyridazinering is fused to a 5 or 6-membered monocyclic heterocyclyl ring havingone or two heteroatoms atoms in the ring, one nitrogen atom togetherwith either one oxygen or one sulfur atom in the ring, or one O or Sring atom.

“Heterocyclylalkyl” refers to an alkyl group, as defined above, whereinone or more of the alkyl group's hydrogen atom has been replaced withheterocyclyl group. Representative examples of a heterocyclylalkyl groupinclude, but are not limited to pyrrolidinyl-1-ethyl-,morpholinyl-1-ethyl-, piperazinyl-1-ethyl-, pyridinylmethyl-,piperidinyl-methyl, or 1-propylpyrrolidine and the like.

The term “heteroatom” as used herein designates a sulfur, nitrogen, oroxygen atom.

“Monocyclic ring” or “Bicyclic ring” refers to a saturated, partiallysaturated or unsaturated 3-12 membered cyclic ring, in which 0 to 4 ringcarbon atoms can be replaced with a heteroatom/heterogroups such as N,O, S, —C(O)—, —S(O), —NH and S(O)₂. Representative examples of a 3 to 12membered ring include, but are not limited to cyclopropyl, cyclohexyl,isoxazole, triazole, imidazol-2-one, oxirane, phenyl, pyridyl, pyrazole,pyrimidine, piperdine, piperazine, thiazole, furan, pyrrolidinyl,pyrazine, pyrrole-2,5-dione, quinoline, morpholine,1,2,3,6-tetrahydropyridine, tetrahydro-2H-pyran,2,3-dihydrobenzo[b][1,4]dioxine, 1H-indazole and the like.

The term “comprise” or “comprising” is generally used in the sense ofinclude, that is to say permitting the presence of one or more featuresor components.

The use of the term “including” as well as other forms, such as“include”, “includes”, and “included”, is not limiting.

As used herein, the terms “treat”, “treating” or “treatment” encompasseither or both responsive and prophylaxis measures, e.g., measuresdesigned to inhibit or delay the onset of the disease or disorder,achieve a full or partial reduction of the symptoms or disease state,and/or to alleviate, ameliorate, lessen, or cure the disease or disorderand/or its symptoms. The terms “treat”, “treating” or “treatment”,include, but are not limited to, prophylactic and/or therapeutictreatments.

As used herein the terms “subject” or “patient” are well-recognized inthe art, and, are used interchangeably herein to refer to a mammal,including dog, cat, rat, mouse, monkey, cow, horse, goat, sheep, pig,camel, and, most preferably, a human. In some embodiments, the subjectis a subject in need of treatment or a subject with a disease ordisorder. However, in other embodiments, the subject can be a normalsubject. The term does not denote a particular age or sex. Thus, adultand new-born subjects, whether male or female, are intended to becovered.

As used herein the term “therapeutically effective amount”, refers to asufficient amount of a compound or a composition being administeredwhich will relieve to some extent one or more of the symptoms of thedisease or condition being treated. The result can be reduction and/oralleviation of the signs, symptoms, or causes of a disease, or any otherdesired alteration of a biological system. The term “therapeuticallyeffective amount” includes, for example, a prophylactically effectiveamount.

“Pharmaceutically acceptable” means that, which is useful in preparing apharmaceutical composition that is generally safe, non-toxic, andneither biologically nor otherwise undesirable and includes that whichis acceptable for veterinary as well as human pharmaceutical use.

“Pharmaceutically acceptable salt” refers to the salts of the compounds,that is pharmaceutically acceptable and that possesses the desiredpharmacological activity of the parent compound. Pharmaceuticallyacceptable salts of the compounds of this invention include thosederived from suitable inorganic and organic acids and bases. Such saltsinclude: acid addition salts, formed with inorganic acids such ashydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like; or formed with organic acids such asacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid,glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid,malic acid, maleic acid, fumaric acid, tartaric acid, citric acid,benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelicacid, methane sulfonic acid, ethane sulfonic acid, 1,2-ethane-disulfonicacid, 2-hydroxyethanesulfonic acid, benzene sulfonic acid,4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid,4-toluenesulfonic acid, camphor sulfonic acid,4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid,3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid,lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxyl naphthoicacid, salicylic acid, stearic acid, muconic acid, and the like.

In further yet another particular embodiment, the compounds andpharmaceutically compositions of the present invention are used in thetreatment and/or prevention of diseases and/or disorders in whichaberrant, abnormal or deregulated activity of bromodomain containingproteins contribute to the pathology and/or symptomology of suchdiseases and/or disorders. Such diseases and/or disorders mediated byone or more of these kinases are provided herein.

In further yet another particular embodiment, the compounds andpharmaceutically compositions of the present invention are useful intreatment and/or prevention of diseases and/or disorders in whichaberrant, abnormal or deregulated activity of BET family of bromodomaincontaining proteins; in particular BRD2, BRD3, BRD4 and BRD-t proteins.

In further yet another particular embodiment, the compounds andpharmaceutically compositions of the present invention are useful inmanufacture of a medicament for use in the treatment of diseasesassociated with bromodomain in animals including humans.

In further yet another particular embodiment, the method of treatment ofdiseases or disease conditions for which bromodomain inhibitor isindicated comprises administering an effective amount of compound offormula (I) according to the present invention.

In further yet another particular embodiment, the disease or diseasecondition for which bromodomain inhibitor is indicated is autoimmune,inflammatory or cancer.

Bromodomain inhibitors are believed to be useful in the treatment of avariety of diseases or conditions related to systemic or tissueinflammation, inflammatory responses to infection or hypoxia, cellularactivation and proliferation, lipid metabolism, fibrosis and in theprevention and treatment of viral infections.

Bromodomain inhibitors may be useful in the treatment of a wide varietyof chronic autoimmune and inflammatory conditions such as rheumatoidarthritis, osteoarthritis, acute gout, psoriasis, systemic lupuserythematosus, multiple sclerosis, inflammatory bowel disease (Crohn'sdisease and Ulcerative colitis), asthma, chronic obstructive airwaysdisease, pneumonitis, myocarditis, pericarditis, myositis, eczema,dermatitis, alopecia, vitiligo, bullous skin diseases, nephritis,vasculitis, atherosclerosis, Alzheimer's disease, depression, retinitis,uveitis, scleritis, hepatitis, pancreatitis, primary biliary cirrhosis,sclerosing cholangitis, Addison's disease, hypophysitis, thyroiditis,type I diabetes and acute rejection of transplanted organs.

Bromodomain inhibitors may be useful in the treatment of a wide varietyof acute inflammatory conditions such as acute gout, giant cellarteritis, nephritis including lupus nephritis, vasculitis with organinvolvement such as glomerulonephritis, vasculitis including giant cellarteritis, Wegener's granulomatosis, Polyarteritisnodosa, Behcet'sdisease, Kawasaki disease, Takayasu's Arteritis, vasculitis with organinvolvement and acute rejection of transplanted organs.

Bromodomain inhibitors may be useful in the prevention or treatment ofdiseases or conditions which involve inflammatory responses toinfections with bacteria, viruses, fungi, parasites or their toxins,such as sepsis, sepsis syndrome, septic shock, endotoxaemia, systemicinflammatory response syndrome (SIRS), multi-organ dysfunction syndrome,toxic shock syndrome, acute lung injury, ARDS (adult respiratorydistress syndrome), acute renal failure, fulminant hepatitis, burns,acute pancreatitis, post-surgical syndromes, sarcoidosis, Herxheimerreactions, encephalitis, myelitis, meningitis, malaria and SIRSassociated with viral infections such as influenza, herpes zoster,herpes simplex and coronavirus.

Bromodomain inhibitors may be useful in the prevention or treatment ofconditions associated with ischaemia-reperfusion injury such asmyocardial infarction, cerebro-vascular ischaemia (stroke), acutecoronary syndromes, renal reperfusion injury, organ transplantation,coronary artery bypass grafting, cardio-pulmonary bypass procedures,pulmonary, renal, hepatic, gastro-intestinal or peripheral limbembolism.

Bromodomain inhibitors may be useful in the treatment of disorders oflipid metabolism via the regulation of APO-A1 such ashypercholesterolemia, atherosclerosis and Alzheimer's disease.

Bromodomain inhibitors may be useful in the treatment of fibroticconditions such as idiopathic pulmonary fibrosis, renal fibrosis,post-operative stricture, keloid formation, scleroderma and cardiacfibrosis.

Bromodomain inhibitors may be useful in the prevention and treatment ofviral infections such as herpes virus, human papilloma virus, adenovirusand poxvirus and other DNA viruses. Bromodomain inhibitors may be usefulin the treatment of cancer, including hematological, epithelialincluding lung, breast and colon carcinomas, midline carcinomas,mesenchymal, hepatic, renal and neurological tumors.

In one embodiment the disease or condition for which a bromodomaininhibitor is indicated is selected from diseases associated withsystemic inflammatory response syndrome, such as sepsis, burns,pancreatitis, major trauma, haemorrhage and ischaemia. In thisembodiment the bromodomain inhibitor would be administered at the pointof diagnosis to reduce the incidence of: SIRS, the onset of shock,multi-organ dysfunction syndrome, which includes the onset of acute lunginjury, ARDS, acute renal, hepatic, cardiac and gastro-intestinal injuryand mortality.

In another embodiment the bromodomain inhibitor would be administeredprior to surgical or other procedures associated with a high risk ofsepsis, haemorrhage, extensive tissue damage, SIRS or MODS (multipleorgan dysfunction syndrome).

In a particular embodiment the disease or condition for which abromodomain inhibitor is indicated is sepsis, sepsis syndrome, septicshock and endotoxaemia. In another embodiment, the bromodomain inhibitoris indicated for the treatment of acute or chronic pancreatitis. Inanother embodiment the bromodomain is indicated for the treatment ofburns. In one embodiment the disease or condition for which abromodomain inhibitor is indicated is selected from herpes simplexinfections and reactivations, cold sores, herpes zoster infections andreactivations, chickenpox, shingles, human papilloma virus, cervicalneoplasia, adenovirus infections, including acute respiratory disease,poxvirus infections such as cowpox and smallpox and African swine fevervirus. In one particular embodiment a bromodomain inhibitor is indicatedfor the treatment of Human papilloma virus infections of skin orcervical epithelia.

The term “diseases or conditions for which a bromodomain inhibitor isindicated”, is intended to include each of or all of the above diseasestates.

While it is possible that for use in therapy, a compound of formula (I)as well as pharmaceutically acceptable salts thereof may be administeredas the raw chemical, it is common to present the active ingredient as apharmaceutical composition.

The term “therapeutically effective amount” means the amount of thesubject compound that will elicit the biological or medical response ofa tissue, system, animal or human that is being sought by theresearcher, veterinarian, medical doctor or other clinician.

The compounds and pharmaceutically compositions of the present inventionmay be used in combination with other drugs that are used in thetreatment/prevention/suppression or amelioration of the diseases orconditions for which compounds of the present invention may be useful.Such other drugs may be administered, by a route and in an amountcommonly used there for, contemporaneously or sequentially with acompound of the present invention. When a compound of the presentinvention is used contemporaneously with one or more other drugs, apharmaceutical composition containing such other drugs in addition tothe compound of the present invention may also be preferred.Accordingly, the pharmaceutical compositions of the present inventioninclude those that also contain one or more other active ingredients, inaddition to a compound of the present invention.

A pharmaceutical composition of the invention may be formulated as beingcompatible with its intended route of administration, which maypreferably be an oral administration. For example the pharmaceuticalcompositions of the invention may be formulated for administration byinhalation, such as aerosols or dry powders; for oral administration,such in the form of tablets, capsules, gels, syrups, suspensions,emulsions, elixirs, solutions, powders or granules; for rectal orvaginal administration, such as suppositories; or for parenteralinjection (including intravenous, subcutaneous, intramuscular,intravascular, or infusion) such as a sterile solution, suspension oremulsion.

The compounds of the present invention may also be entrapped inmicrocapsules prepared, for example, by coacervation techniques or byinterfacial polymerization, for example, hydroxymethyl cellulose orgelatin-microcapsules and poly-(methylmethacylate) microcapsules,respectively, in colloidal drug delivery systems (for example,liposomes, albumin microspheres, microemulsions, nano-particles andnanocapsules) or in macroemulsions. Such techniques are disclosed inRemington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).

The bicyclic heterocyclic derivatives of formula (I) according to thepresent invention may be prepared from readily available startingmaterials using the following general methods and procedures. It will beappreciated that where typical or preferred experimental conditions(i.e. reaction temperatures, time, moles of reagents, solvents etc.) aregiven, other experimental conditions can also be used unless otherwisestated. Optimum reaction conditions may vary with the particularreactants or solvents used, but such conditions can be determined by theperson skilled in the art, using routine optimization procedures. Thespecifics of the processes according to the present invention aredetailed in the example section mentioned below.

In a further aspect, the compounds of the present invention can alsocontain unnatural proportions of atomic isotopes at one or more of theatoms that constitute such compounds. For example, the present inventionalso embraces isotopically-labeled variants of the present inventionwhich are identical to those recited herein, but for the fact that oneor more atoms of the compound are replaced by an atom having the atomicmass or mass number different from the predominant atomic mass or massnumber usually found in nature for the atom. All isotopes of anyparticular atom or element as specified are contemplated within thescope of the compounds of the invention, and their uses. Exemplaryisotopes that can be incorporated in to compounds of the inventioninclude isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous,sulfur, fluorine, chlorine and iodine, such as ²H (“D”), ³H, ¹¹C, ¹³C,¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ¹⁷O, ¹⁸O, ³²P, ³³P, 35S, ¹⁸F, ³⁶Cl, ¹²³I and ¹²⁵I.Isotopically labeled compounds of the present inventions can generallybe prepared by following procedures analogous to those disclosed in theSchemes and/or in the Examples herein below, by substituting anisotopically labeled reagent for a non-isotopically labeled reagent.

The abbreviations used in the entire specification may be summarizedherein below with their particular meaning.

MeOH—Methanol; EtOH—Ethanol; DME—1,2-dimethoxyethane; CHCl₃—Chloroform;DCM—Dichloromethane; DMF—N,N-Dimethylformamide; DMSO—Dimethylsulfoxide;CDCl₃—Deuterated chloroform; EtOAc—Ethylacetate; CH₃CN—Acetonitrile;THF—Tetrahydrofuran; TEA—Triethylamine; DIPEA—Diisopropylethylamine;TFA—Trifluoroacetic acid; AcOH—Acetic acid; AlCl₃—Aluminium chloride;AlBr₃-Aluminium bromide; Br₂—Bromine; NBS—N-bromosuccinimide;NCS—N-chlorosuccinimide; MeI—Methyl iodide; KI—Potassium iodide;TPP—Triphenyl phosphene; NaOAc—Sodiumacetate; KOAc—Potassiumacetate;Na₂SO₄—Sodium sulphate; H₂SO₄—Sulfuric acid; HNO₃—Nitric acid;HBr-Hydrobromic acid; NaHCO₃—Sodium bicarbonate; KHCO₃—Potassiumbicarbonate; Na₂CO₃—Sodium carbonate; K₂CO₃—Potassium carbonate;Cs₂CO₃—Cesiumcarbonate; NaH—Sodium hydride; t-BuOK—Potassiumtert-butoxide; LDA—lithium diisopropylamide; n-BuLi—n-Butyllithium;DIAD—Diisopropylazodicarboxylate; BBr₃—Boron tribromide; NMP—N-Methylpyrrolidine; DAST—Diethylaminosulfurtrifluoride; AgBF₄—Silvertetrafluoroborate; NaN₃—Sodium azide; CuI—Copper(I)iodide;SnCl₂.2H₂O—Stannous chloride dihydrate; NaBH₄—Sodium borohydride;NaCNBH₃—Sodium cyanoborohydride; (BOC)₂O—Di-tert-butyldicarbonate;EDC.HCl-|-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride;HOBt—1-hydroxybenzotriazole; POCl₃—Phosphorous oxychloride;SOCl₂—Thionyl chloride; AcCl—Acetyl chloride; Ac₂O—Acetic anhydride;NH₄Cl—Ammonium chloride; NiCl₂—Nickel chloride; H₂O₂—Hydrogen peroxide;NaOEt—Sodium ethoxide; NaOMe—Sodium methoxide; NaOH—Sodium hydroxide;KOH—potassium hydroxide; HCl—Hydrochloric acid; Pd(pph₃)₄—Tetrakis(triphenylphosphine)palladium(O); Pd(dppf)Cl₂—[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex withdichloromethane; Pd(OAc)₂—Palladium(II)acetate;BINAP—2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene;TMS-CF₃-(Trifluoromethyl)trimethylsilane; TBAF—Tetrabutylammoniumfluoride; KCN—Potassium cyanide; Pd/C-Palladium on activated carbon;H₂O—Water; Fe—Iron powder; ML—Milliliter; TLC—Thin layer chromatography;RT—Room temperature; h—Hour; N—Normality; M—Molarity; s—Singlet;d—Doublet; t—Triplet; m—Multiplet; ¹HNMR-Proton nuclear magneticresonance; MS—Mass spectroscopy; LC—Liquid chromatography; H—Proton;MHz—Mega hertz; Hz—Hertz; ppm—Parts per million; Bs—Broad singlet;ES—Electro spray; Conc—Concentrated; g—Gram and Mmol—Milli mol.

General Scheme:

In one aspect of the present invention relates to the preparation ofbicyclic heterocyclic derivatives of formula (I). Herein disclosed thegeneral process for preparation of the compound of formula (I).

In Scheme-I, the compounds of formula-I are prepared in two methods:Method-I:

N-alkylation/sulfonamide formation followed by Suzuki coupling.

Method-II:

Suzuki coupling followed by N-alkylation/sulfonamide formation.

N-Alkylation/Sulfonamide Formation:

The compound of formula-1.0 and 1.2 can undergoN-alkylation/sulfonylation with sulfonyl chloride/sulfonates/alkylhalidederivatives in presence of a suitable solvent (e.g., ACN, DMF, DCM, THF,Dioxane, and the like) and a suitable base (e.g., Cs₂CO₃, t-BuOK, K₂CO₃,Na₂CO₃, Pyridine, and the like) at a temperature of about 0° C. to 50°C. for about 2-48 h to provide compound of formula-1.1 and compound offormula (I) respectively.

Suzuki Coupling:

A compound of formula (I) and a compound of formula-1.2 can be preparedby reacting a compound of formula-1.1 and a compound of formula-1.0 withCy₁-boronic acid/ester respectively in presence of a suitable solvent(e.g., DME/H₂O, 1,4-Dioxane/H₂O, DMF, DMSO, and the like), a suitablebase (e.g., Na₂CO₃, K₂CO₃, KOAc, and the like) and a suitable Pdcatalyst (e.g., Pd(OAc)₂, Pd(PPh₃)₂Cl₂, Pd(PPh₃)₄, Pd(dppf)₂Cl₂, and thelike) at a temperature of about 60° C. to 150° C. for about 2 to 24 h.

Method-III: (De-Alkylation):

The compound of formula-I (2.0) can be treated with strong acid (e.g.,BBr₃, HCl, HBr, and the like) in presence of a suitable solvent (e.g.,DCM, CHCl₃, DCE or 1,4-Dioxane, and the like) at a temperature of about−78° C. to 35° C. for about 2 to 24 h to provide the compound offormula-I (2.1).

Method-IV:

This method can be carried out in any of the alternative proceduresgiven below.

O-alkylation:

The compound of formula-I (2.1) can undergo O-alkylation with R₁—Br inpresences of a suitable solvent (e.g., DMF, ACN, THF, Dioxane, and thelike) and a suitable base (e.g., NaH, Cs₂CO₃, t-BuOK, K₂CO₃, Na₂CO₃,Pyridine, and the like) at a temperature of about 20° C. to 120° C. forabout 2 to 48 h to provide the compound of formula (I).

Mitsunobu or Mitsunobu-Type Reaction:

The compound of formula-I (2.1) can be treated with R₁—OH in presence oftriphenylphosphine, and suitable reagent like DIAD or DEAD in a suitablesolvent (e.g., Diethyl ether, THF, and the like) at a temperature ofabout 0° C. to 35° C. for about 8 to 24 h to provide the compound offormula (I).

EXAMPLES

Although the invention has been illustrated by certain of the precedingexamples, it is not to be construed as being limited thereby; butrather, the invention encompasses the generic area as hereinbeforedisclosed. Various modifications and embodiments can be made withoutdeparting from the spirit and scope thereof.

The MS data provided in the examples described below were obtained asfollows:

Mass spectrum: LC/MS Agilent 6120 Quadrapole LC/MS.

The NMR data provided in the examples described below were obtained asfollows:

¹H-NMR: Varian 400 MHz.

The microwave chemistry was performed on a CEM Explorer.

The procedure for the compounds of Formula (I) are detailed herein belowstepwise including the general Synthesis of various intermediatesinvolved in process of manufacture of the compounds according to thepresent invention.

Intermediate-1: Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine

Step-a: Synthesis of 2-amino-4-methoxyphenol

To a solution of 4-methoxy-2-nitrophenol (5.0 g, 29.58 mmol) in MeOH (50mL) was added 10% Pd—C (2.5 g) and stirred under H₂ balloon pressure atRT for 16 h. After completion of the reaction, the reaction mixture wasfiltered through celite bed, washed with methanol. The filtrate wasconcentrated to afford the title product as an off white solid (4.0 g,97%). The crude product was as such taken forward for next step withoutfurther purification. ¹H NMR (400 MHz, CDCl₃): δ 6.75-6.60 (m, 1H),6.40-6.28 (m, 1H), 6.25-6.15 (m, 1H), 3.75-3.60 (bs, 3H); LC-MS: m/z140.1 (M+1)⁺.

Step-b: Synthesis of 2-acetamido-4-methoxyphenylacetate

To an ice-cooled solution of 2-amino-4-methoxyphenol (5 g, 35.97 mmol)in THF (130 mL) was added triethylamine (25 mL, 179.85 mmol) and stirredfor 10 min before acetyl chloride (7.7 mL, 107.91 mmol) was added. Thenthe reaction mixture allowed to stir at RT for 16 h. After completion ofthe reaction, the reaction mixture was quenched with NaHCO₃ solution (upto pH ˜8) and extracted with EtOAc (200 mL×2). The combined organiclayers were washed with water (200 mL), brine (100 mL), dried oversodium sulphate and concentrated to get residue. The residue wasdirectly used for next step without further purification (5.0 g, 62%).¹H NMR (400 MHz, CDCl₃): δ 7.90-7.75 (bs, 1H), 7.25-7.10 (m, 1H),7.05-6.95 (m, 1H), 6.70-6.60 (m, 1H), 3.79 (s, 3H), 2.34 (s, 3H), 2.17(s, 3H); LC-MS: m/z 224.1 (M+1)⁺.

Step-c: Synthesis of 2-acetamido-5-bromo-4-methoxyphenylacetate

To an ice cooled solution of 2-acetamido-4-methoxyphenyl acetate (5.0 g,22.42 mmol) in DMF (65 mL) was add N-bromosuccinimide (4.79 g, 26.90mmol) portion wise and stirred at RT for 16 h. After completion of thereaction, the reaction mixture was poured over crushed ice, separatedsolids were filtered, washed with water and dried under reducedpressure. The residue was directly used for next step without furtherpurification (4.0 g, 59%). ¹H NMR (400 MHz, CDCl₃): δ 7.99 (s, 1H), 7.33(s, 1H), 7.20-7.10 (bs, 1H), 3.89 (s, 3H), 2.36 (s, 3H), 2.19 (s, 3H);LC-MS: m/z 302.0 (M+1)⁺.

Step-d: Synthesis N-(4-bromo-2-hydroxy-5-methoxyphenyl)acetamide

To a solution of 2-acetamido-5-bromo-4-methoxyphenyl acetate (1.0 g,3.29 mmol) in MeOH (10 mL) was add potassium carbonate (1.36 g, 9.86mmol) portion wise and stirred at RT for 16 h. After completion of thereaction, the reaction mixture was poured over crushed ice, separatedsolids were filtered, washed with water and dried under vacuum. Theresidue was directly used for the next step without further purification(0.7 g, 81%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.70 (s, 1H), 9.31 (s, 1H),7.69 (s, 1H), 7.02 (s, 1H), 3.71 (s, 3H), 2.09 (s, 3H); LC-MS: m/z 262.0(M+1)⁺.

Step-e: Synthesis1-(7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanone

To a solution of N-(4-bromo-2-hydroxy-5-methoxyphenyl)acetamide (0.60 g,2.30 mmol) in DCM (7.5 mL) and CH₃CN (4.5 mL) were added1,2-dibromoethane (0.8 mL, 9.23), NaOH (037 g, 9.23 mmol),benzyltriethylammonium chloride (0.12 g) and stirred at RT for 16 h.After completion of the reaction, the reaction mixture was diluted withwater (80 mL) and extracted with EtOAc (200 mL). The organic layer waswashed with water (200 mL), brine (100 mL), dried over sodium sulphateand concentrated to afford the title compound as an off white solid (0.5g, 75%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.05-7.80 (bs, 1H), 7.12 (s, 1H),4.21 (t, J=4.4 Hz, 2H), 3.83 (t, J=4.6 Hz, 2H), 3.74 (s, 3H), 2.27 (s,3H); LC-MS: m/z 288.0 (M+1)⁺.

Step-f: Synthesis 1-(7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanone

To a solution of1-(7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanone (0.45 g,1.57 mmol) in 1,2-DME (4.5 mL) and H₂O (1.5 mL) were added3,5-dimethylisoxazole boronic acid (0.66 g, 4.72 mmol), sodium carbonate(0.42 g, 3.93 mmol) and degassed with nitrogen purging for 20 min. Thentetrakistriphenylphosphinepalladium(0) (0.09 g, 0.078 mmol) was addedand heated at 100° C. for 16 h. After completion of the reaction, thereaction mixture was diluted with EtOAc (50 mL), washed with water (50mL), brine (50 mL), dried over sodium sulphate and concentrated to getresidue. The obtained residue was directly used for next step, withoutfurther purification (0.3 g, 66%). ¹H NMR (400 MHz, DMSO-d₆): δ8.00-7.80 (bs, 1H), 6.76 (s, 1H), 4.23 (t, J=4.4 Hz, 2H), 3.87 (t, J=4.6Hz, 2H), 3.68 (s, 3H), 2.30 (s, 3H), 2.25 (s, 3H), 2.07 (s, 3H); LC-MS:m/z 303.1 (M+1)⁺.

Step-g: Synthesis 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine

To a solution of1-(7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanone(0.3 g, 0.99 mmol) in MeOH (3 mL) and H₂O (1 mL) was added KOH (0.35 g,6.35 mmol) and stirred at RT for 2 h. Reaction mixture was diluted withEtOAc (50 mL), washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The obtained residue was directly usedfor next step, without further purification (0.2 g, 77%); LC-MS: m/z261.1 (M+1)⁺.

Intermediate-2: Synthesis of7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one

Step-a: Synthesis of 6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one

To an ice-cooled solution of 2-amino-4-methoxyphenol (4 g, 28.77 mmol)in CH₃CN (50 mL) was added K₂CO₃ (12.0 g, 86.33 mmol) and stirred for 10min before 2-chloroacetyl chloride (3.43 g, 57.55 mmol) was added. Thenthe reaction mixture was allowed stirred at 100° C. for 2 h. Aftercompletion of the reaction, the reaction was concentrated and treatedwith ice-cold water to crash out the solids. The separated solids werefiltered, washed with water and dried under vacuum (4.1 g, 78%). ¹H NMR(400 MHz, DMSO-d₆): δ 10.61 (bs, 1H), 6.87-6.85 (m, 1H), 6.50-6.47 (m,2H), 4.48 (s, 2H), 3.68 (s, 3H); LC-MS: m/z 178.2 (M−1)⁺.

Step-b: Synthesis of 7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one

To an ice cooled solution of 6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(4.0 g, 22.9 mmol) in DMF (50 mL) was add N-bromosuccinimide (10.17 g,58.0 mmol) portion wise and stirred at RT for 3 h. After completion ofthe reaction, the reaction mixture was poured over ice water, separatedsolids were filtered, washed with water and dried under vacuum (4.0 g,70%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.72 (bs, 1H), 7.19 (s, 1H), 6.62(s, 1H), 4.53 (s, 2H), 3.76 (s, 3H); LC-MS: m/z 257.0 (M−1)⁺.

Intermediate-3: Synthesis of7-bromo-6-methoxy-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

The process for preparation is similar to the one depicted inintermediate-2. The desired compound obtained as a white solid (0.09 g,60%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.64 (bs, 1H), 7.15 (s, 1H), 6.61(s, 1H), 3.76 (s, 3H), 1.37 (s, 6H).

Intermediate-4: Synthesis of7-amino-4-(4-chlorobenzyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one

Step-a: Synthesis of 6-methoxy-7-nitro-2H-benzo[b][1,4]oxazin-3 (4H)-one

To an ice cooled solution of 6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(0.60 g, 3.35 mmol) in AcOH (1.8 mL) was added drop wise 70% HNO₃ (0.6mL) and stirred at RT for 15 min. After completion of the reaction, thereaction mixture was poured into ice water (100 g), separated solidswere filtered, washed with water and dried under reduced pressure. Theresidue was directly used for the next step without further purification(0.60 g, 80%). ¹H NMR (400 MHz, DMSO-d₆) δ 11.14 (bs, 1H), 7.60 (s, 1H),6.75 (s, 1H), 4.64 (s, 2H), 3.85 (s, 3H). LC-MS: m/z 223.1 (M−1)⁺.

Step-b: Synthesis of4-(4-chlorobenzyl)-6-methoxy-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one

To an solution of 6-methoxy-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one(0.60 g, 2.67 mmol) in DMF (6 mL) were added K₂CO₃ (1.06 g, 7.68 mmol),followed by addition of 4-chloro benzyl bromide (0.41 g, 2.00 mmol), andstirred at 80° C. for 16 h. After completion of the reaction, thereaction mixture was poured into ice water (100 g), separated solidswere filtered, washed the solid thoroughly with water and dried underreduced pressure. The residue was directly used for the next stepwithout further purification (0.48 g, 51%). ¹H NMR (400 MHz, DMSO-d₆) δ7.63 (s, 1H), 7.43-7.37 (m, 4H), 6.89 (s, 1H), 5.29 (s, 2H), 4.86 (s,2H), 3.78 (s, 3H).

Step-c: Synthesis of7-amino-4-(4-chlorobenzyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one

To a solution of4-(4-chlorobenzyl)-6-methoxy-7-nitro-2H-benzo[b][1,4]oxazin-3 (4H)-one(0.48 g, 1.38 mmol) in EtOH (5 mL) and water (2.5 mL) at RT were addedNH₄Cl (0.22 g, 4.14 mmol) followed by Fe powder (0.39 g, 7.00 mmol) andrefluxed at 100° C. for 2 h. Then the reaction mixture was cooled to RT,filtered through celite pad and washed with EtOAc (200 mL). The organiclayer was washed with aq. sodium bicarbonate solution (50 mL), water (50mL), brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified by column chromatography on silica gel (100-200mesh) to afford the title compound (0.20 g, 46%); ¹H NMR (400 MHz,DMSO-d₆) δ 7.39 (d, J=8.3 Hz, 2H), 7.31 (d, J=8.3 Hz, 2H), 6.54 (s, 1H),6.31 (s, 1H), 5.10 (s, 2H), 4.66 (s, 2H), 4.58 (s, 2H), 3.60 (s, 3H);LC-MS: m/z 319.1 (M+1)⁺.

Intermediate-5: Synthesis of 6-bromo-7-methoxyquinolin-2(1H)-one

Step-a: Synthesis of 3,3-diethoxypropanoic acid

To a stirred suspension of ethyl 3,3-diethoxypropanoate (15.0 g, 78.88mmol) in water (32 mL) was added NaOH (4.10 g, 102.6 mmol) and heated to110° C. for 1.5 h. After completion of the reaction, the reactionmixture was cooled, acidified to pH˜3 with aq. 3N HCl and extracted withEtOAc (500 mL×2). The organic layer was washed with water (200 mL),brine (100 mL), dried over sodium sulphate and concentrated. The residuewas used for next step without further purification (11.50 g, 91%). ¹HNMR (400 MHz, DMSO-d₆): δ 12.20 (s, 1H), 4.81 (t, J=5.9 Hz, 1H),3.58-3.59 (m, 2H), 3.48-3.40 (m, 2H), 2.60-2.40 (m, 2H), 1.09 (t, J=7.3Hz, 6H).

Step-b: Synthesis of 3-ethoxyacryloyl chloride

To an ice cooled compound of 3,3-diethoxypropanoic acid (5.00 g, 31.05mmol) was added thionyl chloride (10.0 mL, 142.9 mmol) over a period of10 min., and stirred at 80° C. for 1.5 h. After completion of thereaction, the reaction mixture was concentrated and dried under reducedpressure to afford the title product as a dark brown liquid (3.0 g,73%). ¹H NMR (400 MHz, DMSO-d₆): δ 7.50 (d, J=12.2 Hz, 1H), 5.14 (d,J=12.2 Hz, 1H), 3.94 (q, J=7.3 Hz, 2H), 1.24 (t, J=7.3 Hz, 3H).

Step-c: Synthesis of(E/Z)—N-(4-bromo-3-methoxyphenyl)-3-ethoxyacrylamide

To an ice cooled solution of 4-bromo-3-methoxyaniline (3.00 g, 14.85mmol) in pyridine (20 mL) was added (E/Z)-3-ethoxyacryloyl chloride(2.98 g, 22.27 mmol) over a period of 5 min. and stirred at RT for 16 h.After completion of the reaction, the reaction mixture was diluted withice cooled water and extracted with EtOAC (150 mL×2). The combinedorganic layer was washed with aq. 1N HCl (100 mL), water (150 mL), brine(100 mL), dried over sodium sulphate and concentrated. The residue wasused for next step without further purification (3.20 g, 72%). 15 ¹H NMR(400 MHz, DMSO-d₆): δ 9.86 (s, 1H), 7.54-7.42 (m, 3H), 7.12-7.08 (m,1H), 5.50 (d, J=12.7 Hz, 1H), 3.95 (q, J=6.9 Hz, 2H), 3.80 (s, 3H), 1.27(t, J=7.3 Hz, 3H); LC-MS: m/z 301.1 (M+1)⁺.

Step-d: Synthesis of 6-bromo-7-methoxyquinolin-2(1H)-one

A solution of (E/Z)—N-(4-bromo-3-methoxyphenyl)-3-ethoxyacrylamide (3.0g, 10.0 mmol) in Conc. H₂SO₄ (30 mL) was stirred at RT for 1 h. Aftercompletion of the reaction, the reaction mixture was poured over icewater; separated solids were filtered, washed the solid thoroughly withwater and dried under reduced pressure. The residue was directly usedfor the next step without further purification (2.08 g, 82%). ¹H NMR(400 MHz, DMSO-d₆): δ 12.70 (bs, 1H), 7.94 (s, 1H), 7.80 (d, J=9.8 Hz,1H), 6.92 (s, 1H), 6.36 (d, J=9.8 Hz, 1H), 3.88 (s, 3H); LC-MS: m/z256.0 (M+1)⁺.

Intermediate-6: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one

Step-a: Synthesis of 4-(3,5-dimethylisoxazol-4-yl)-3-methoxyaniline

The process of this step was adopted from step-f of intermediate-1. Thedesired compound obtained as a pale yellow solid (0.6 g, 60%). ¹H NMR(400 MHz, DMSO-d₆): δ 6.78 (d, J=7.8 Hz, 1H), 6.30-6.19 (m, 2H), 5.26(s, 2H), 3.66 (s, 3H), 2.19 (s, 3H), 2.02 (s, 3H); LC-MS: m/z 219.2(M+1)⁺.

Step-b: Synthesis of(E)-N-(4-(3,5-dimethylisoxazol-4-yl)-3-methoxyphenyl)-3-ethoxyacrylamide

The process of this step was adopted from step-c of intermediate-5. Thedesired compound obtained as a pale yellow solid (0.4 g, 46%). ¹H NMR(400 MHz, DMSO-d₆): δ 9.85 (s, 1H), 7.52-7.48 (m, 2H), 7.22-7.21 (m,1H), 7.11-7.09 (m, 1H), 5.53 (d, J=12.2 Hz, 2H), 3.98-3.93 (m, 2H), 3.73(s, 3H), 2.23 (s, 3H), 2.05 (s, 3H), 1.30-1.22 (m, 2H); LC-MS: m/z 317.2(M+1)⁺.

Step-c: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one

The process of this step was adopted from step-d of intermediate-5. Thedesired compound obtained as an off white solid (0.2 g, 59%); ¹H NMR(400 MHz, DMSO-d₆): δ 11.76 (bs, 1H), 7.82 (d, J=9.3 Hz, 1H), 7.53 (s,1H), 6.94 (s, 1H), 6.35 (d, J=9.8 Hz, 1H), 3.81 (s, 3H), 2.26 (s, 3H),2.07 (s, 3H); LC-MS: m/z 271.1 (M+1)⁺.

Intermediate-7: Synthesis of6-bromo-7-methoxy-3-methylquinolin-2(1H)-one

Step-a: Synthesis of (E)-ethyl3-(4-methoxy-2-nitrophenyl)-2-methylacrylate

To a stirred suspension of sodium hydride (0.44 g, 11.04 mmol) in THF(20 mL) at 0° C. were added 4-methoxy-2-nitrobenzaldehyde (1.0 g, 5.52mmol) and ethyl-2-(triphenyl phosphoranylidene)propanoate (2.0 g, 5.52mmol), allowed to stir at RT for 4 h. After completion of the reaction,the reaction mixture diluted with water and extracted with EtOAc (200mL×2). The combined organic layers were washed with water (200 mL),brine (100 mL), dried over sodium sulphate and concentrated. The residuewas purified on silica gel (100-200 mesh) to afford the title product asa brown solid (0.33 g, 22%). ¹H NMR (400 MHz, CDCl₃): δ 7.83 (s, 1H),7.63 (d, J=2.4 Hz, 1H), 7.26 (s, 1H), 7.20-7.17 (m, 1H), 4.28 (q, J=7.3Hz, 2H), 3.90 (s, 3H), 1.91 (s, 3H), 1.35 (t, J=7.4 Hz, 3H).

Step-b: Synthesis of (E)-ethyl3-(2-amino-4-methoxyphenyl)-2-methylacrylate

To a solution of (E)-ethyl 3-(4-methoxy-2-nitrophenyl)-2-methylacrylate(0.33 g, 1.23 mmol) in MeOH (10 mL) were added Conc. HCl (2.0 mL) andSnCl₂.2H₂O (1.46 g, 6.05 mmol) stirred at 80° C. for 4 h. Aftercompletion of the reaction, the reaction mixture was filter throughcelite, the filtrate was concentrated. The residue was diluted withwater and extracted with EtOAc (200 mL×2). The combined organic layerswere washed with water (200 mL), brine (100 mL), dried over sodiumsulphate and concentrated under reduced pressure. The residue waspurified by column chromatography by using silica gel (100-200 mesh) toafford the title product as a brown solid (0.2 g, 69%). ¹H NMR (400 MHz,DMSO-d₆): δ 7.50 (s, 1H), 7.01 (d, J=8.3 Hz, 1H), 6.29 (d, J=2.3 Hz,1H), 6.19 (dd, J=8.8, 2.4 Hz, 1H), 5.24 (bs, 2H), 4.20-4.10 (m, 2H),3.68 (s, 3H), 1.95 (s, 3H), 1.25 (d, J=6.8 Hz, 3H); LC-MS: m/z 236.2(M+1)⁺.

Step-c: Synthesis of 7-methoxy-3-methylquinolin-2(1H)-one

A solution of (E)-ethyl 3-(2-amino-4-methoxyphenyl)-2-methylacrylate(0.13 g, 0.55 mmol) in dioxane.HCl (4 mL) was heated at 100° C. in asealed tube for 16 h. After completion of the reaction, the reactionmixture was allowed to RT and concentrated, neutralized with cold aq.NaHCO₃ solution. The residue was extracted with EtOAc (200 mL×2) twice.The combined organic layers were washed with water (200 mL), brine (100mL), dried over sodium sulphate and concentrated under reduced pressureto afford the title product as an off white solid (0.06 g, 58%). ¹H NMR(400 MHz, DMSO-d₆): δ 11.59 (bs, 1H), 7.67 (s, 1H), 7.48 (d, J=8.3 Hz,1H), 6.79-6.75 (m, 2H), 3.79 (s, 3H), 2.04 (s, 3H); LC-MS: m/z 190.2(M+1)⁺.

Step-d: Synthesis of 6-bromo-7-methoxy-3-methylquinolin-2(1H)-one

The process of this step was adopted from step-b of Intermediate-2. Thedesired compound obtained as an off white solid (0.06 g, 53%); ¹H NMR(400 MHz, DMSO-d₆): δ 11.72 (bs, 1H), 7.84 (s, 1H), 7.66 (s, 1H), 6.91(s, 1H), 3.87 (s, 3H), 2.04 (s, 3H); LC-MS: m/z 268.0 (M+1)⁺.

Alternative Procedure Synthesis of6-bromo-7-methoxy-3-methylquinolin-2(1H)-one

Step-a: Synthesis of N-(3-methoxyphenyl)acetamide

To an ice-cooled solution of 3-methoxyaniline (40 g, 325.0 mmol) in AcOH(40 mL) was added aceticanhydride (40 mL) drop wise and stirred at RTfor 2 h. Reaction mixture was poured into ice water; solid was filteredoff and washed with water, dried under reduced pressure for overnight togive title compound as off white solid (60 g). ¹H NMR (400 MHz, DMSO-d₆)δ 9.89 (s, 1H), 7.27 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.09 (d, J=8.3 Hz,1H), 6.60 (dd, J=2.2 Hz, 8.2 Hz, 1H), 3.71 (s, 3H), 2.02 (s, 3H); LC-MS:m/z 166.2 (M+1)⁺.

Step-b: Synthesis of 2-chloro-7-methoxyquinoline-3-carbaldehyde

POCl₃ (339 mL, 3636.0 mmol) was added drop wise to DMF (112 mL, 1454.4mmol) at 0° C., after stirred for 5 min, N-(3-methoxyphenyl)acetamide(60 g, 363.6 mmol) was added and resulting solution was heated to 100°C. for 3 h. The reaction mixture was cooled to room temperature andpoured into ice water; solid was filtered off and washed with water,dried under reduced pressure for overnight to give title compound aspale yellow solid (88 g). ¹H NMR (400 MHz, DMSO-d₆) δ 10.34 (s, 1H),8.88 (s, 1H), 8.18 (d, J=8.8 Hz, 1H), 7.45 (d, J=2.5 Hz, 1H), 7.39 (dd,J=2.5 Hz, 9.3 Hz, 1H), 3.98 (s, 3H); LC-MS: m/z 222.1 (M+1)⁺.

Step-c: Synthesis of 7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde

A suspension of 2-chloro-7-methoxyquinoline-3-carbaldehyde (8.0 g, 36.2mmol) in 70% acetic acid (370 mL) was heated to 110° C. for 16 h. Uponcooling the reaction mixture to room temperature and poured into crushedice; solid was filtered off and washed with water, dried under reducedpressure for overnight to give title compound as pale yellow solid (5.6g, 76%). ¹H NMR (400 MHz, DMSO-d₆) δ 12.07 (s, 1H), 10.18 (s, 1H), 8.43(s, 1H), 7.84 (d, J=8.9 Hz, 1H), 6.89 (dd, J=2.5 Hz, 8.8 Hz, 1H), 6.82(d, J=1.9 Hz, 1H), 3.86 (s, 3H); LC-MS: m/z 204.1 (M+1)⁺.

Step-d: Synthesis of 7-methoxy-3-methylquinolin-2(1H)-one

To an ice-cooled solution of7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (6 g, 29.55 mmol) inTFA (110 mL) was added triethyl silane (13.2 mL) drop wise and stirredat RT for 16 h. Reaction mixture was poured into ice water; solid wasfiltered off and washed with water, dried under reduced pressure forovernight to give title compound as pale yellow solid crude (6 g). ¹HNMR (400 MHz, DMSO-d₆) δ 11.59 (s, 1H), 7.67 (s, 1H), 7.48 (d, J=8.8 Hz,1H), 6.78-6.75 (m, 2H), 3.78 (s, 3H), 2.04 (s, 3H); LC-MS: m/z 190.1(M+1)⁺.

Step-e: Synthesis of 6-bromo-7-methoxy-3-methylquinolin-2(1H)-one

The process of this step was adopted from step-b of Intermediate-2.

Intermediate-7.1 Synthesis of6-bromo-3-cyclohexyl-7-methoxyquinolin-2(1H)-one

Step-a: Synthesis of methyl3-(5-bromo-4-methoxy-2-nitrophenyl)-2-cyclohexyl-3-hydroxy propanoate

To a solution of methyl 2-cyclohexylacetate (0.39 g, 2.49 mmol) in THF(20 mL) at −78° C. was added LDA 2.0 M in THF (2.4 mL, 4.80 mmol) andstirred for 1 h at same conditions, then added5-bromo-4-methoxy-2-nitrobenzaldehyde (0.5 g, 1.92 mmol) in THF andstirred at −78° C. for 2 h. The reaction mixture quenched with sat NH₄Cland extracted with EtOAc (150 mL) and washed with water (150 mL), driedover sodium sulphate and concentrated under reduced pressure. Theresidue was used for further step without purification (0.07 g crude).

Step-b: Synthesis of 6-bromo-3-cyclohexyl-7-methoxyquinolin-2(1H)-one

To a solution of methyl3-(5-bromo-4-methoxy-2-nitrophenyl)-2-cyclohexyl-3-hydroxy propanoate(0.5 g, 1.29 mmol) in AcOH (10 mL) was added iron powder (0.2 g, 3.88mmol) and stirred at 80° C. for 1 h. Reaction mixture filtered throughcelite, washed with EtOAc combined filtrate was concentrated, theresidue was diluted with water and extracted with EtOAc (100 mL), washedwith brine (100 mL), dried over sodium sulphate and concentrated. Theresidue was used for further step without purification (crude-0.4 g). ¹HNMR (400 MHz, DMSO-d₆): δ 11.70 (s, 1H), 7.89 (s, 1H), 7.59 (s, 1H),6.89 (s, 1H), 3.86 (s, 3H), 2.67-2.55 (m, 1H), 1.83-1.77 (m, 6H),1.34-1.23 (m, 4H); LC-MS: m/z 336.1 (M+1)⁺.

Intermediate-8: Synthesis of6-bromo-7-methoxy-4-methylquinolin-2(1H)-one

Step-a: Synthesis of N-(4-bromo-3-methoxyphenyl)-3-oxobutanamide

To a stirred solution of 4-bromo-3-methoxyaniline (0.5 g, 2.47 mmol) intoluene (5 mL) were added ethylacetoacetate (0.5 mL, 3.71), sodiumethoxide (0.34 g, 4.94 mmol), and heated to 110° C. for 16 h. Aftercompletion of the reaction, the reaction mixture was diluted with EtOAC(100 mL), washed with water (100 mL), brine (100 mL), dried over sodiumsulphate and concentrated. The residue was purified by columnchromatography by using silica gel (60-120 mesh) to afford the titleproduct as yellow solid (0.4 g, 90%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.21(s, 1H), 7.48-7.43 (m, 2H), 7.11-7.08 (m, 1H), 3.83 (s, 3H), 3.54 (s,2H), 2.20 (s, 3H); ES-MS: m/z 286.1 (M+1)⁺.

Step-b: Synthesis of 6-bromo-7-methoxy-4-methylquinolin-2(1H)-one

The process of this step was adopted from step-d of intermediate-5. Thedesired compound obtained as a pale yellow solid (0.33 g, 90%); ¹H NMR(400 MHz, DMSO-d₆): δ 11.56 (bs, 1H), 7.86 (s, 1H), 6.93 (s, 1H), 6.26(s, 1H), 3.88 (s, 3H), 2.37 (s, 3H); LC-MS: m/z 268.1 (M+1)⁺.

The below Intermediates 9 and 10 were prepared according to the aboveprotocol.

Int Characterization No. Structure data  9

LC-MS: m/z 323.3 (M + 1)⁺. 10

LC-MS: m/z 297.0 (M + 1)⁺.

Intermediate-11: Synthesis of6-bromo-7-methoxy-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one

Step-a: Synthesis of N-(4-bromo-3-methoxyphenyl)-3-methylbut-2-enamide

A solution of 4-bromo-3-methoxyaniline (2.0 g, 9.90 mmol) in chloroform(20 mL) was added 3-methylbut-2-enoyl chloride and refluxed for 3 h.After completion of the reaction, the reaction mixture was poured overcold aq. NaHCO₃ solution and extracted with EtOAC (50 mL), washed withwater (50 mL), brine (50 mL), dried over sodium sulphate andconcentrated. The residue was used for next step without furtherpurification (1.7 g). ¹H NMR (400 MHz, DMSO-d₆): δ 9.95 (s, 1H), 7.56(d, J=2.5 Hz, 1H), 7.44 (d, J=8.3 Hz, 1H), 7.11 (dd, J=2.2, 8.4 Hz, 1H),5.84 (s, 1H), 3.80 (s, 3H), 2.14 (s, 3H), 1.84 (s, 3H); LC-MS: m/z 284.0(M+1)⁺.

Step-b: Synthesis of6-bromo-7-methoxy-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one

N-(4-bromo-3-methoxyphenyl)-3-methylbut-2-enamide (0.5 g, 1.76 mmol) washeated at 130° C. before aluminum chloride (0.35 g, 2.64 mmol) was addedportion wise over a period of 1.5 h. After completion of the reaction,the reaction mixture was diluted with H₂O (50 mL), extracted with EtOAc(100 mL×2). The combined organic layers were washed with water (50 mL),brine (50 mL), dried over sodium sulphate and concentrated. The residuewas purified by column chromatography by using silica gel (100-200 mesh)to afford the title product as a off-white solid. (0.15 g, 31%). ¹H NMR(400 MHz, DMSO-d₆): δ 10.14 (bs, 1H), 7.38 (s, 1H), 6.62 (s, 1H), 3.77(s, 3H), 2.32 (s, 2H), 1.19 (s, 6H); ES-MS: m/z 285.0 (M+1)⁺.

Intermediate-12: Synthesis of6-bromo-7-methoxy-3,3-dimethylquinoline-2,4(1H,3H)-dione

Step-a: Synthesis of3-((3-methoxyphenyl)amino)-2,2-dimethyl-3-oxopropanoicacid

A solution of 2,2-dimethylmalonic acid (5.3 g, 40.65 mmol) and thionylchloride (3.5 mL, 48.78 mmol) in THF (20 mL) was refluxed for 2 h andthen concentrated. The residue was dissolved in THF (20 mL) and solutionwas slowly added into a solution of 3-methoxy aniline (5 g, 40.65 mmol)and triethylamine (5.6 mL, 40.65 mmol) in THF (20 mL) at 0° C., then thereaction mixture allowed to stir at RT for 1 h. After completion of thereaction, the reaction mixture concentrated and diluted with 5N NaOHsolution (p^(H)˜9-11), washed with EtOAc. The aqueous layer wasacidified with Conc. HCl and the resulting precipitate was collected andwashed with water to afford the title product as a white solid (2.5 g,29%). ¹H NMR (400 MHz, DMSO-d₆): δ 12.65 (bs, 1H), 9.41 (s, 1H), 7.33(t, J=1.9 Hz, 1H), 7.24-715 (m, 2H), 6.63-6.60 (m, 1H), 3.71 (s, 3H),1.40 (s, 6H); ES-MS: m/z 236.1 (M−1)⁻.

Step-b: Synthesis of 7-methoxy-3,3-dimethylquinoline-2,4(1H,3H)-dione

A solution of 3-((3-methoxyphenyl)amino)-3-oxopropanoic acid (0.5 g,2.39 mmol) in poly phosphoric acid (5 mL) was heated to 130° C. for 4 h.After completion of the reaction, the reaction mixture was poured intoice water and extracted with EtOAc (100 mL). The organic layer waswashed with brine (100 mL), dried over sodium sulphate and concentrated.The residue was purified on silica gel (60-120 mesh) to afford the titleproduct as a yellow solid (0.25 g, 54%); ES-MS: m/z 220.1 (M+1)⁺.

Step-c: Synthesis of6-bromo-7-methoxy-3,3-dimethylquinoline-2,4(1H,3H)-dione

The process of this step was adopted from step-b of intermediate-2. Thedesired compound obtained as white solid 0.15 g (73%); ¹H NMR (400 MHz,DMSO-d₆): δ 10.80 (s, 1H), 7.84 (s, 1H), 6.74 (s, 1H), 3.91 (s, 3H),1.33 (s, 6H); LC-MS: m/z 299.1 (M+1)⁺.

Intermediate-13: Synthesis of6-bromo-7-methoxy-3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one

Step-a: Synthesis of7-methoxy-3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one

To a stirred solution of7-methoxy-3,3-dimethylquinoline-2,4(1H,3H)-dione (0.25 g, 1.14 mmol) inAcOH (28 mL), were added Ac₂O (0.12 mL), Conc. H₂SO₄ (0.02 mL), 10% Pd—Cthen hydrogenated using hydrogen bladder pressure at RT for 16 h. Thenthe reaction mixture filtered, powdered NaHCO₃ was added to the filtrateand extracted with EtOAc (100 mL) and organic layer washed with water(100 mL), dried over sodium sulphate and concentrated. The residue waspurified by column chromatography by using silica gel (60-120 mesh) toafford the title product as a pale yellow solid (0.15 g, 65%). ¹H NMR(400 MHz, DMSO-d₆): δ 9.91 (s, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.50-6.43(m, 2H), 3.68 (s, 3H), 2.65 (s, 2H), 1.03 (s, 6H); LC-MS: m/z 206.2(M+1)⁺.

Step-b: Synthesis of6-bromo-7-methoxy-3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one

The process of this step was adopted from step-b of intermediate-2. Thedesired compound obtained as a white solid (0.09 g, 60%). ¹H NMR (400MHz, DMSO-d₆): δ 10.03 (s, 1H), 7.34 (s, 1H), 6.60 (s, 1H), 3.76 (s,3H), 2.68 (s, 2H), 1.03 (s, 6H); LC-MS: m/z 286.1 (M+1)⁺.

Intermediate-14: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one

Step-a: Synthesis of 6-bromo-7-hydroxy-3, 4-dihydroquinolin-2(1H)-one

The process of this step was adopted from step-b of intermediate-2. Thedesired compound obtained as a white solid (2.2 g, 75%); ¹H NMR (400 MHzDMSO-d₆) δ 9.46 (bs, 1H), 9.39 (bs, 1H), 7.18 (s, 1H), 6.56 (s, 1H),2.82 (t, J=7.3 Hz, 2H), 2.52 (t, J=7.3 Hz, 2H); ES-MS m/z 244.1 (M+1)⁺.

Step-b: Synthesis of 6-bromo-7-methoxy-3, 4-dihydroquinolin-2(1H)-one

To a stirred suspension of 6-bromo-7-hydroxy-3,4-dihydroquinolin-2(1H)-one (2.2 g, 9 mmol) in ethanol was added K₂CO₃(2.49 g, 18.1 mmol). The resulting mixture was refluxed for 2 h, thenreaction mixture cooled to 0° C. and methyl iodide (2.5 g, 18.1 mmol),KI (0.075 g, 18.1 mmol) were added. The reaction mixture was refluxedfor 12 h, filtered, concentrated under reduced pressure. The residue waspurified by chromatography on silica (10% EtOAc in hexanes) to give thedesired product as a off-white solid (1.7 g, 73%). ¹H NMR (400 MHzDMSO-d₆) δ 10.07 (bs, 1H), 7.30 (s, 1H), 6.60 (s, 1H), 3.76 (s, 3H),2.81-2.78 (m, 2H), 2.43-2.40 (m, 2H); ES-MS m/z 256.1 (M+1)⁺.

Step-c: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one

The process of this step was adopted from step-f of intermediate-1. Thedesired compound obtained as an off white solid (0.150 g, 47%). ¹H NMR(400 MHz DMSO-d₆) δ 10.09 (s, 1H), 6.99 (s, 1H), 6.62 (s, 1H), 3.69 (s,3H), 3.82 (t, J=7.6 Hz, 2H), 2.45 (t, J=7.6 Hz, 2H), 2.23 (s, 3H), 2.05(s, 3H); ES-MS m/z 273.1 (M+1)⁺.

Intermediate-15: Synthesis of 1-(pyridin-4-yl)ethylmethanesulfonate

Step-a

To an ice cooled solution of 1-(pyridin-4-yl)ethanol (0.25 g, 2.07 mmol)in DCM (5 mL) were added triethylamine (0.58 mL, 4.14 mmol) followed bymethanesulfonylchloride (0.32 mL, 4.14 mmol) and stirred at RT for 4 h.After completion of the reaction, the reaction mixture was diluted withDCM (50 mL) and washed with water (50 mL), brine (20 mL), dried oversodium sulphate and concentrated. The residue was used for next stepwithout further purification (0.42 g, 100%). ¹H NMR (400 MHz, DMSO-d₆):δ 8.61 (d, J=6.0 Hz, 2H), 7.44 (d, J=6.0 Hz, 2H), 5.80 (qt, J=6.8 Hz,1H), 3.20 (s, 3H), 1.60 (d, J=6.8 Hz, 3H); LC-MS: m/z 202.1 (M+1)⁺.

The below Intermediates 16 to 26, 26a, 26b, 26c and 26d were preparedaccording to the above protocol.

Int Characterization No. Structure data 16

— 17

LC-MS: m/z 202.1 (M + 1)⁺. 18

LC-MS: m/z 221.1 (M + 1)⁺. 19

— 20

LC-MS: m/z 206.1 (M + 1)⁺. 21

— 22

— 23

ES-MS: m/z 202.1 (M + 1)⁺. 24

— 25

ES-MS: m/z 189.1 (M + 1)⁺. 26

ES-MS: m/z 194.1 (M + 1)⁺. 26a

LC-MS: m/z 218.1 (M + 1)⁺. 26b

— 26c

— 26d

—

Intermediate-27: Synthesis of 2-(iodomethyl)-5-(trifluoromethyl)pyridine

To a stirred solution of (5-(trifluoromethyl)pyridin-2-yl)methanol (0.9g, 5.02 mmol) in anhydrous THF (10 mL), triphenylphosphine (1.97 g, 7.54mmol), imidazole (1.02 g, 15.08 mmol) and iodine (1.92 g, 7.54 mmol)were added sequentially at RT. The reaction mixture was stirred for 30min at room temperature. After complete of the reaction, the reactionmixture was quenched with an aqueous sodium thiosulfate (20 mL). Theorganic solvent was separated and aqueous layer was extracted withdiethyl ether. The combined organic layer were washed with brinesolution and dried over anhydrous Na₂SO₄. The solvents were removedunder reduced pressure. The residue was purified by columnchromatography (60-120 silica gel and 2% EtOAc in hexane as eluent) toyield the title compound (0.30 g, 20%). ¹H NMR, CDCl₃, 300 MHz: δ 8.82(s, 1H), 7.86 (dd, J=8.1 & 1.8 Hz, 1H), 7.51 (d, J=8.1 Hz, 1H), 4.55 (s,2H); LC-MS: m/z 287.8 (M+1)⁺.

Intermediate-28: Synthesis of7-bromo-6-methoxy-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one(Method-A)

To a solution of intermediate-2 (0.5 g, 1.98 mmol) in CH₃CN (20 mL) wereadded cesium carbonate (1.58 g, 4.85 mmol) followed by4-(bromomethyl)pyridine.HBr (0.73 g, 2.91 mmol) and stirred at 60° C.for 6 h. After completion of the reaction, the reaction mixture wasconcentrated, diluted with water and extracted with EtOAc (200 mL×2)twice. The combined organic layers were washed with water (200 mL),brine (100 mL), dried over sodium sulphate and concentrated underreduced pressure. The residue was purified on silica gel (100-200 mesh)to afford the titled product as off-white solid (0.52 g, 74%). ¹H NMR(400 MHz, DMSO-d₆) δ 8.52 (d, J=4.4 Hz, 2H), 7.31-7.30 (m, 3H), 6.89 (s,1H), 5.26 (s, 2H), 4.78 (s, 2H), 3.66 (s, 3H).

Intermediate-29: Synthesis of6-bromo-1-((6-chloropyridin-3-yl)methyl)-7-methoxyquinolin-2(1H)-one(Method-B)

To a solution of intermediate-5 (0.2 g, 0.78 mmol) in DMF (5 mL) wereadd potassium carbonate (0.32 g, 0.99 mmol) followed by2-chloro-5-(chloromethyl)pyridine (0.33 g, 2.36 mmol) and stirred at RTfor 16 h. After completion of the reaction, the reaction mixture wasdiluted with water and extracted with EtOAc (200 mL×2). The combinedorganic layers were washed with water (200 mL), brine (100 mL), driedover sodium sulphate and concentrated. The residue was purified bypreparative TLC to afford the title product as an off white solid (0.05g, 17%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.44 (d, J=2.5 Hz, 1H), 8.04 (s,1H), 7.90 (d, J=9.3 Hz, 1H), 7.67 (dd, J=5.9 & 2.4 Hz, 1H), 7.46 (d,J=8.3 Hz, 1H), 6.98 (s, 1H), 6.60 (d, J=9.3 Hz, 1H), 5.60 (s, 2H), 3.86(s, 3H); LC-MS: m/z 379.0 (M+1)⁺.

Intermediate-30: Synthesis of6-bromo-7-methoxy-1-(pyrimidin-4-ylmethyl)quinolin-2(1H)-one (Method-C)

To a stirred solution of intermediate-5 (0.15 g, 0.59 mmol) in DMF (5mL) were added 60% NaH (0.035 g, 0.088 mmol), 4-(chloromethyl)pyrimidine(0.113 g, 0.88 mmol), and stirred at RT for 16 h. After completion ofthe reaction, the reaction mixture was poured on ice water, diluted withEtOAC (30 mL), washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The residue was purified on silica gel(100-200 mesh) to afford the titled product as off-white solid (0.08 g,39%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.07-9.06 (m, 1H), 8.73 (d, J=4.8 Hz,1H), 8.04 (s, 1H), 7.94-7.90 (m, 1H), 7.41-7.39 (m. 1H), 6.94 (s, 1H),6.57 (d, J=9.8 Hz, 1H), 5.66 (s, 2H), 3.80 (s, 3H); LC-MS: m/z 346.1(M+1)⁺.

The below intermediates were prepared by using the above three differentmethods. This N-alkylation reaction can be carried out by using theappropriate reactant having alkylhalide/mesylate in presence of suitablebase.

Int No. Structure Method Characterization data 31

A ¹H NMR (400 MHz, CDCl₃) δ 7.40-7.10 (m, 5H), 6.39 (s, 1H), 5.12 (s,2H), 4.67 (s, 2H), 3.67 (s, 3H); ES-MS: m/z 382.1 (M + H)⁺. 32

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.56 (d, J = 6.0 Hz, 2H), 7.36 (d, J =5.2 Hz, 2H), 7.32 (s, 1H), 6.37 (s, 1H), 6.15-60.5 (m, 1H), 4.74-4.65(m, 2H), 3.52 (s, 3H), 1.79 (d, J = 6.8 Hz, 3H); LC-MS: m/z 364.1.0 (M +1)⁺. 33

A ¹H NMR (400 MHz, CDCl₃): δ 8.63-8.56 (m, 2H), 7.59 (d, J = 8.0 Hz,1H), 7.31-7.29 (m, 1H), 7.21 (s, 1H), 6.41 (s, 1H), 5.18 (s, 2H), 4.68(s, 2H), 3.69 (s, 3H); LC-MS: m/z 351.0 (M + 1)⁺. 34

A ¹H NMR (400 MHz, CDCl₃) δ 8.56 (d, J = 4.0 Hz, 1H), 7.66 (td, J = 7.6& 2.0 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 7.23-7.20 (m, 1H), 7.17 (s,1H), 6.89 (s, 1H), 5.26 (s, 2H), 4.66 (s, 2H), 3.74 (s, 3H); LC-MS: m/z349.0 (M + 1)⁺. 35

A ¹H NMR (400 MHz, DMSO-d₆): δ 7.26 (s, 1H), 6.94 (s, 1H), 4.60 (s, 2H),3.92 (d, J = 7.2 Hz, 2H), 3.86 (s, 3H), 3.81 (dd, J = 11.6 & 2.8 Hz,2H), 3.21 (t, J = 5.8 Hz, 2H), 1.94-1.89 (m, 1H), 1.52-1.48 (m, 2H),1.30-1.18 (m, 2H); LC-MS: m/z 358.1 (M + 1)⁺. 36

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.60 (d, J = 2.4 Hz, 1H), 8.50 (d, J =4.4 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.40 (dd, J = 8.4 & 3.6 Hz, 1H),7.30 (s, 1H), 6.45 (s, 1H), 6.14 (q, J = 7.6 Hz, 1H), 4.73-4.63 (m, 2H),3.54 (s, 3H), 1.83 (d, J = 7.6 Hz, 3H); LC-MS: m/z 364.0 (M + 1)⁺. 37

A 1H NMR (400 MHz, CDCl₃): δ 8.13 (d, J = 2.4 Hz, 1H), 7.50 (dd, J = 8.8& 2.8 Hz, 1H), 7.19 (s, 1H), 6.72 (d, J = 8.4 Hz, 1H), 6.51 (s, 1H),5.08 (s, 2H), 4.64 (s, 2H), 3.91 (s, 3H), 3.74 (s, 3H). LC-MS: m/z 381.0(M + 1)⁺. 38

A ¹H NMR (400 MHz, CDCl₃): δ 8.84 (d, J = 2.0 Hz, 1H), 7.95 (dd, J = 7.6& 2.0 Hz, 1H), 7.49 (d, J = 6.0 Hz, 1H), 7.21 (s, 1H), 6.76 (s, 1H),5.29 (s, 2H), 4.66 (s, 2H), 3.77 (s, 3H); LC-MS: m/z 376.0 (M + 1)⁺. 39

A ¹H NMR (400 MHz, CDCl₃): δ 8.51 (d, J = 2.4 Hz, 1H), 7.64 (dd, J = 8.8& 2.4 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.17 (s, 1H), 6.90 (s, 1H),5.21 (s, 2H), 4.64 (s, 2H), 3.70 (s, 3H); LC-MS: m/z 384.0 (M + 1)⁺. 40

A ¹H NMR (400 MHz, CDCl₃) δ 8.41 (s, 1H), 7.45-7.35 (m, 2H), 7.17 (s,1H), 6.95 (s, 1H), 5.23 (s, 2H), 4.64 (s, 2H), 3.79 (s, 3H); LC-MS: m/z367.0 (M + 1)⁺. 41

A ¹H NMR (400 MHz, CDCl₃) δ 8.23 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 8.8Hz, 1H), 7.18-7.15 (m, 2H), 7.03 (s, 1H), 5.19 (s, 2H), 4.63 (s, 2H),3.84 (s, 3H), 3.79 (s, 3H); LC- MS: m/z 381.0 (M + 1)⁺. 42

A ¹H NMR (400 MHz, CDCl₃) δ 8.59-8.58 (m, 1H), 7.81- 7.77 (m, 1H),7.43-7.41 (m, 1H), 7.33-7.26 (m, 1H), 7.13 (s, 1H), 6.61 (s, 1H),6.23-6.18 (m, 1H), 4.66 (s, 2H), 3.54 (s, 3H), 1.80 (d, J = 6.9 Hz, 3H);LC-MS: m/z 365.0 (M + 1)⁺. 43

A LC-MS: m/z 363.0 (M + 1)⁺. 44

A ¹H NMR (400 MHz, DMSO-d₆): δ 7.45-7.35 (m, 4H), 6.40 (s, 1H),6.13-6.11 (m, 1H), 4.72-4.63 (m, 2H), 4.04-4.02 (m, 1H), 3.51 (s, 3H),1.78 (d, J = 6.9 Hz, 3H); ES-MS: m/z 398.1 (M + 1)⁺. 45

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.52 (d, J = 4.4 Hz, 1H), 7.71-7.67 (m,1H), 7.29-7.21 (m, 3H), 6.94 (s, 1H), 4.57 (s, 2H), 4.30 (t, J = 7.0 Hz,2H), 3.86 (s, 3H), 3.05 (t, J = 7.0 Hz, 2H); LC-MS: m/z 363.0 (M + 1)⁺.46

A ¹H NMR (400 MHz, CDCl₃) δ 7.32 (s, 1H), 6.59 (s, 1H), 4.60 (s, 2H),4.25-4.14 (m, 2H), 4.15-3.80 (m, 5H), 2.75-2.60 (m, 2H), 2.00-1.90 (m,1H), 1.75-1.70 (m, 2H), 1.47 (s, 9H), 1.40-1.25 (m, 2H). 47

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.59 (d, J = 1.5 Hz, 1H), 8.46 (dd, J =3.9 & 1.0 Hz, 1H), 8.04 (s, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.60 (d, J =7.8 Hz, 1H), 7.35-7.32 (m, 1H), 6.99 (s, 1H), 6.60 (d, J = 9.8 Hz, 1H),5.61 (s, 2H), 3.84 (s, 3H); LC-MS: m/z 346.0 (M + 1)⁺. 48

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.57-8.55 (m, 1H), 8.18-8.15 (m, 2H),7.79-7.75 (m, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.32-7.27 (m, 1H), 7.18 (s,1H), 6.99 (d, J = 8.8 Hz, 1H), 6.45-6.44 (m, 1H), 3.95 (s, 3H), 1.67 (d,J = 6.8 Hz, 3H); LC-MS: m/z 361.0 (M + 1)⁺. 49

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.75 (s, 1H), 8.50- 8.48 (m, 1H),8.18-8.14 (m, 2H), 7.93-7.90 (m, 1H), 7.41-7.38 (m, 1H), 7.22 (s, 1H),6.95 (d, J = 8.8 Hz, 1H), 6.48-6.42 (m, 1H), 3.97 (s, 3H), 1.68 (d, J =6.4 Hz, 3H); LC-MS: m/z 359.0 (M + 1)⁺. 50

A LC-MS: m/z 359.1 (M + 1)⁺. 51

A ¹H NMR (400 MHz, DMSO-d₆): δ 8.49 (d, J = 3.0 Hz, 1H), 8.01 (s, 1H),7.87 (d, J = 9.6 Hz, 1H), 7.72-7.67 (m, 1H), 7.42-7.38 (m, 1H), 7.07 (s,1H), 6.57 (d, J = 9.6 Hz, 1H), 5.63 (s, 2H), 3.82 (s, 3H); LC-MS: m/z365.0 (M + 1)⁺. 52

A ¹H NMR (400 MHz DMSO-d₆): δ 8.41 (d, J = 8.8 Hz, 1H), 8.23-8.21 (m,2H), 8.01 (t, J = 9.3 Hz, 2H), 7.80- 7.78 (m, 1H), 7.69 (d, J = 8.3 Hz,1H), 7.63 (m, 1H), 7.27 (s, 1H), 7.08 (d, J = 8.8 Hz, 1H), 5.76 (s, 2H),3.97 (s, 3H); LC-MS: m/z 395.0 (M + 1)⁺. 53

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 2.5 Hz, 1H), 8.01 (s, 1H),7.90-7.87 (m, 2H), 7.36 (d, J = 8.8 Hz, 1H), 7.04 (s, 1H), 6.57 (d, J =9.8 Hz, 1H), 5.63 (s, 2H), 3.81 (s, 3H); LC-MS: m/z 380.1 (M + 1)⁺. 54

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.74-8.73 (m, 1H), 8.02 (s, 2H), 7.86 (d,J = 9.2 Hz, 1H), 7.41-7.38 (m, 1H), 6.88 (s, 1H), 6.54 (d, J = 8.8 Hz,1H), 5.73 (s, 2H), 3.75 (s, 3H); LC-MS: m/z 348.0 (M + 1)⁺. 55

B ES-MS: m/z 367.1 (M + 1)⁺. 56

B LC-MS: m/z 353.0 (M + 1)⁺. 57

B ¹H NMR (CDCl₃, 300 MHz): δ 8.82 (s, 1H), 7.85 (d, J = 7.2 Hz, 1H),7.71 (s, 1H), 7.59 (d, J = 9.6 Hz, 1H ), 7.47 (d, J = 8.1 Hz, 1H), 7.11(s, 1H), 6.66 (d, J = 9.6 Hz, 1H), 5.71 (bs, 2H), 3.91 (s, 3H); LC-MS:m/z 414.8 (M + 1)⁺. 58

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 7.2 Hz, 1H), 7.77-7.73 (m,1H), 7.40 (s, 1H), 7.34-7.25 (m, 2H), 6.81 (s, 1H), 5.28 (s, 2H), 3.67(s, 3H), 2.55 (s, 2H), 1.23 (s, 6H); LC-MS: m/z 377.1 (M + 1)⁺. 59

B ES-MS: m/z 377.0 (M + 1)⁺. 60

B ¹H NMR (400 MHz, CDCl₃): δ 8.56 (d, J = 4.9 Hz, 1H), 7.63-7.58 (m,2H), 7.46 (s, 1H), 7.26-7.24 (m, 1H), 7.20-7.18 (m, 1H), 7.12 (s, 1H),5.68 (s, 2H), 3.86 (s, 3H), 2.29 (s, 3H); LC-MS: m/z 361.0 (M + 1)⁺. 61

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.55 (d, J = 2.0 Hz, 1H), 7.91-7.87 (m,2H), 7.75 (d, J = 1.0 Hz, 1H), 7.35 (d, J = 8.8 Hz, 1H), 7.02 (s, 1H),5.65 (s, 2H), 3.80 (s, 3H), 2.13 (s, 3H); LC-MS: m/z 393.0 (M + 1)⁺. 62

B ¹H NMR (400 MHz, CDCl₃): δ 7.67 (s, 1H), 7.43 (s, 1H), 7.30-7.26 (m,2H), 7.22 (d, J = 8.3 Hz, 2H), 6.66 (s, 1H), 4.45 (t, J = 7.9 Hz, 2H),3.93 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H), 2.24 (s, 3H); LC-MS: m/z 406.0(M + 1)⁺. 63

B LC-MS: m/z 427.1 (M + H, 97.56%). 64

B LC-MS: m/z 429.1 (M + 2)²⁺. 65

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 4.4 Hz, 1H), 7.92 (s, 1H),7.79-7.75 (m, 1H), 7.39-7.37 (m, 1H), 7.31-7.28 (m, 1H), 6.90 (s, 1H),5.38 (s, 2H), 3.80 (s, 3H), 2.40 (s, 6H); LC-MS: m/z 391.0 (M + 1)⁺. 66

B LC-MS: m/z 375.1 (M + 1)⁺. 67

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 4.4 Hz, 1H), 7.92 (s, 1H),7.76-7.72 (m, 1H), 7.29-7.24 (m, 2H), 7.07 (s, 1H), 6.50 (s, 1H), 5.61(s, 2H), 3.78 (s, 3H), 2.42 (s, 3H); LC-MS: m/z 359.1 (M + 1)⁺. 68

B ¹H NMR (400 MHz, DMSO-d₆): δ 8.49-8.48 (m, 1H), 7.81-7.77 (m, 2H),7.42-7.40 (m, 1H), 7.31-7.29 (m, 1H), 7.22 (s, 1H), 7.10 (s, 1H), 5.71(s, 2H), 3.84 (s, 3H); LC-MS: m/z 413.0 (M + 1)⁺. 69

B ¹H NMR (400 MHz, CDCl₃): δ 8.55 (d, J = 4.5 Hz, 1H), 8.18 (s, 1H),7.59 (dt, J = 7.8, 1.8 Hz, 1H), 7.25 (s, 1H), 7.20-7.17 (m, 2H), 7.15(s, 1H), 5.64 (bs, 2H), 3.87 (s, 3H), 2.10-2.00 (m, 1H), 1.23-1.07 (m,2H), 0.83-0.78 (m, 2H); LC-MS: m/z 385.1 (M + 1)⁺. 70

C ¹H NMR (400 MHz, DMSO-d₆): δ 8.49 (d, J = 4.4 Hz, 1H), 8.01 (s, 1H),7.87 (d, J = 9.2 Hz, 1H), 7.78-7.77 (m, 1H), 7.29-7.26 (m, 2H), 7.08 (s,1H), 6.58 (d, J = 9.2 Hz, 1H), 5.62 (s, 2H), 3.79 (s, 3H); MS (ES) m/e347.0 (M + 2)²⁺. 71

C ¹H NMR 400 MHz (DMSO-d₆) δ 8.02 (s, 1H), 7.96 (S, 1H), 7.40-7.39 (m,2H), 7.38-7.30 (m, 2H), 6.93 (S, 1H), 6.60 (d, J = 9.2 Hz, 1H), 5.56 (s,2H), 3.82 (S, 3H); MS (LC) m/e 378.0 (M + 1)⁺.

Intermediate-72: Synthesis of tert-butyl3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

To a stirred solution of3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(0.5 g, 2.25 mmol) in 1,4-dioxane (10.0 mL) and 2M Na₂CO₃ solution (2.5mL) was added Boc-anhydride (0.62 mL, 2.70 mmol) and stirred at RT for48 h. After completion of the reaction, the reaction mixture was dilutedwith EtOAc (200 mL), washed with water (100 mL), brine (50 mL), driedover sodium sulphate and concentrated. The residue was purified onsilica gel (100-200 mesh) to isolate the title compound as off-whitesolid (0.45 g, 62%). ¹H NMR (400 MHz, DMSO-d₆) δ 3.31 (s, 3H), 2.21 (s,3H), 1.55 (s, 9H), 1.26 (s, 12H); LC-MS: m/z 323.2 (M+1)⁺.

Intermediate-73: Synthesis of3-bromo-1-(3,4-dimethoxybenzyl)-4-methyl-1H-pyrrole-2,5-dione

Step-a: Synthesis of 3-bromo-4-methylfuran-2,5-dione

A stirred mixture of 3-methyl-2,5-furandione (2.0 g, 17.85 mmol), AlBr₃(0.11 g, 3.18 mmol) and Br₂ (1.6 mL, 71.4 mmol) was heated overnight at120° C. Upon completion of reaction, the reaction mixture was cooled toRT and diluted with ethyl acetate (100 mL). The organic phase was washedwith 0.1% HCl and brine. The organic phase were dried over anhydrousNa₂SO₄ and concentrated under reduced pressure to obtain crude compound,which was used in next step without any purification (3.20 g, crude). ¹HNMR (300 MHz, CDCl₃): δ 2.21 (s, 3H).

Step-b: Synthesis of3-bromo-1-(3,4-dimethoxybenzyl)-4-methyl-1H-pyrrole-2,5-dione

A stirred solution of 3-bromo-4-methyl-2,5-furandione (1.0 g, 5.29 mmol)in acetic acid (10 mL) was treated with1-[3,4-bis(methyloxy)phenyl]methanamine (0.8 g, 5.29 mmol) at RT. Theresulting mixture was heated overnight at 100° C. Upon completion of thereaction (TLC), the reaction mixture was concentrated under reducedpressure. The obtained residue was taken in AcOH (20 mL) and AcONa(0.315 g, 4.23 mmol) was added to the above solution. The reactionmixture was refluxed for 2 h. The reaction mixture was cooled to RT anddiluted with cold water, before extracting with DCM (3×50 mL). Thecombined organic phase was dried over anhydrous Na₂SO₄ and concentratedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (elution 10% EtOAc/hexanes) to give the titlecompound as off-white solid (1.0 g, 55.8%). ¹H NMR (300 MHz, CDCl₃): δ6.95-6.92 (m, 2H), 6.81-6.77 (m, 1H), 4.62 (s, 2H), 3.87 (s, 3H), 3.85(s, 3H), 2.03 (s, 3H); LC-MS: m/z 341.8 (M+1)⁺.

Intermediate-74: Synthesis of3-cyclopropyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole

Step-a: Synthesis of Cyclopropanecarbaldehydeoxime

To a stirred solution of hydroxylamine hydrochloride (3.0 g, 45 mmol) inwater (10 mL) were added Na₂CO₃ (2.4 g, 18 mmol) and a solution ofcyclopropanecarboxaldehyde (2.1 g, 30 mmol) in ethyl alcohol (9 mL) atRT. Then the reaction mixture was stirred at room temperature for 2 hand was extracted with ethyl acetate. The combined organic extracts werewashed with brine, dried over anhydrous sodium sulfate and concentrated.The product was re-crystalyzed with hexane as white crystalline needles(2.20 g, 99%). ¹H NMR (400 MHz, CDCl₃): δ 8.60 (bs, 1H), 6.03 (d, J=8.8Hz, 1H), 2.31-2.27 (m, 1H), 0.97-0.83 (m, 2H), 0.65-0.61 (m, 2H); LC-MS:m/z 86.2 (M+1)⁺.

Step-b: Synthesis of N-hydroxycyclopropanecarbimidoyl chloride

To a stirred solution of cyclopropanecarbaldehyde oxime (1.0 g, 11.75mmol) in DMF (10 mL) maintained at RT, NCS (1.50 g, 27.74 mmol) wasadded under argon atmosphere at RT and stirred for 2 h. The reactionmixture was diluted with water and extracted with DCM (3×50 mL). Thecombined organic extract was washed with brine and concentrated underreduced pressure. The residue obtained was used in next step withoutfurther purification (1.00 g, crude); ¹H NMR (400 MHz, CDCl₃): δ 9.92(bs, 1H), 1.91-1.87 (m, 1H), 0.94-0.90 (m, 2H), 0.80-0.75 (m, 2H).

Step-c: Synthesis of3-cyclopropyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole

A stirred solution of N-hydroxycyclopropanecarbimidoyl chloride (0.5 g,4.20 mmol) in DME (16 mL) was treated with4,4,5,5-tetramethyl-2-(prop-1-yn-1-yl)-1,3,2-dioxaborolane (0.69 g, 4.2mmol) and KHCO₃ (0.84 g, 8.4 mmol) at RT under a nitrogen atmosphere.The reaction mixture was heated at 50° C. for 12 h. The mixture wascooled to room temperature and filtered through celite pad. The filtratewas concentrated under reduced pressure. The obtained oily residue waspurified by silica gel (100-200 mesh) column chromatography (using10-20% EtOAc/Hexane as eluent) to give the title compound as a whitesolid (0.5 g); LC-MS: m/z 249.8 (M+1)⁺.

Intermediate-75: Synthesis of3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trimethylsilyl)isoxazole

Step-a: Synthesis oftrimethyl((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethynyl)silane

To a stirred solution of trimethylsilylacetylene (5.27 g, 53.76 mmol) inTHF (100 mL) at −78° C., 2.5 M of n-BuLi in n-hexane (35.3 mL, 53.76mmol) was added drop wise under nitrogen atmosphere. After 15 min,2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (10.0 g, 53.76mmol) was slowly added and the reaction mixture was stirred at −78° C.After 2 h, the reaction mixture was allowed to warm to −30° C., and thep^(H) was adjusted to 3 using anhydrous HCl. The reaction mixture wasfiltered, and the filtrate was distilled to give the title product(10.00 g, crude). ¹H NMR (400 MHz, DMSO-d₆): δ 1.17 (s, 12H), 0.14 (s,9H).

Step-b: Synthesis of3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trimethylsilyl)isoxazole

A solution of chloroacetaldoxime (0.5 g, 4.62 mmol),trimethyl((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethynyl)silane(0.833 g, 3.73 mmol) and KHCO₃ (0.934 g, 9.35 mmol) in DME (16 mL) washeated at 50° C. for 12 h. After completion of the reaction, thereaction mixture was cooled to room temperature, solids were filteredthrough celite. The filtrate was concentrated under reduced pressure togive yellow oil, which was purified by flash column chromatography (10%EtOAc/Hexane as eluent) to give the title compound as a white solid(0.60 g, 45.5%). ¹H NMR (CDCl₃, 300 MHz): δ2.40 (s, 3H), 1.31 (s, 12H),0.37 (s, 9H); LC-MS: m/z 282.3 (M+1)⁺.

Intermediate-76: Synthesis of7-methoxy-1-(pyridin-2-ylmethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2(1H)-one

In a resealable reaction tube, to a solution of6-bromo-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one (1.0 g, 2.90mmol) in 1, 4-dioxane, was added4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.1 g, 4.30mmol), Pd(dppf)Cl₂.DCM (0.23 g, 0.29 mmol), and KOAc (0.85 g, 8.7 mmol)under nitrogen atmosphere. The solution was degassed with nitrogen gasfor 15 min, later gradually heated to 100° C. and stirred at sametemperature until the completion of reaction. The reaction mixture wascooled to room temperature, was diluted with cold water and extractedwith ethyl acetate (3×30 mL). The combined organic layers were washedwith brine and concentrated under reduced pressure. The residue obtainedwas purified by column chromatography (60-120 mesh, 50-100%EtOAc-hexanes as eluent) to yield the title compound as a pale brownsolid (0.80 g, 70.7%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (s, 1H),7.94-7.90 (m, 2H), 7.78 (m, 1H), 7.3-7.19 (m, 2H), 6.87 (s, 1H),6.56-6.45 (m, 1H), 5.60 (d, J=18.8 Hz, 2H), 3.93 (s, 3H), 1.26 (s, 12H);LC-MS: m/z 393.2 (M+1)⁺.

Intermediate-77: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinoxalin-2(1H)-one

Step-a: Synthesis of ethyl2-((5-bromo-4-methoxy-2-nitrophenyl)amino)acetate

To a suspension of 5-bromo-4-methoxy-2-nitroaniline (1 g, 4.0 mmol) inethylbromo acetate (8 g, 4.7 mmol) was added K₂CO₃ (0.838 g, 6.1 mmol).The reaction mixture was heated to 150° C. and maintained for 3 h atsame temperature. The reaction mixture was diluted with ethyl acetateand washed with water (50 mL×3) and dried over Na₂SO₄ and concentration.The obtained residue was purified by column chromatography on silica(2-5% EtOAc in hexane) to give the desired product as an off white solid(0.600 g, 45%). ¹HNMR (400 MHz, DMSO-d₆) δ 8.25 (bs, 1H), 7.63 (s, 1H),7.32 (s, 1H), 4.29 (d, J=6.0 Hz, 2H), 4.17 (q, J=7.0 Hz, 2H), 3.84 (s,3H), 1.22 (t, J=7.0 Hz, 3H). MS (ES) m/e 333.1 (M+1)⁺.

Step-b: Synthesis of ethyl2-((5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitrophenyl)amino)acetate

To a stirred solution of ethyl2-((5-bromo-4-methoxy-2-nitrophenyl)amino)acetate (1 g, 3.0 mmol) in 10mL of 1,4-Dioxane:H₂O (7:3) was added3,5-dimethylisoxazole-4-boronicacid (0.847 g, 6.0 mmol), K₂CO₃ (1.243 g,9.0 mmol), followed by Pd(PPh₃)₂Cl₂ (0.210 g, 0.3 mmol). The reactionmixture was heated to 100° C. and maintained for 1.5 h at sametemperature. Then allowed to RT and reaction mixture was diluted withethyl acetate and washed with water (50 mL×3), dried over Na₂SO₄ andconcentration to gave the desired product as a white solid (0.7 g, 67%);MS (ES) m/e 350.2 (M+1)⁺.

Step-c: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinoxalin-2(1H)-one

A stirred solution of ethyl2-((5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitrophenyl) amino)acetate(0.07 g, 2.0057 mmol) in 10 mL of ethanol was added SnCl₂.2H₂O (2.25 g,10.028 mmol). The reaction mixture was heated to reflux and maintainedfor 1 h. The reaction mixture was basified with aq. Na₂CO₃, extractedwith ethyl acetate and dried under reduced pressure to afford the titlecompound (0.500 g, 97%) as pale brown solid. ¹HNMR (400 MHz, DMSO-d₆) δ12.4 (bs, 1H), 10.3 (s, 1H), 8.03 (s, 1H), 7.64 (s, 1H), 3.85 (s, 3H),3.63 (s, 2H), 2.28 (s, 3H), 2.23 (s, 3H). MS (ES) m/e 274.2 (M+1)⁺.

Step-d: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinoxalin-2(1H)-one

A stirred solution of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinoxalin-2(1H)-one(0.200 g, 0.7782 mmol) in 8% NaOH (2.64 mL) solution was added 30%H₂O₂(2.34 mL) at room temperature. The reaction mixture was heated to80° C. and maintained for 4 h at same temperature. The reaction mixturewas cooled and acetic acid (0.3 mL) was added drop wise. The suspensionwas stirred over night at room temperature and the precipitated solidwas collected by filtration to afford the title compound as an off whitesolid (0.117 g, 59%). ¹HNMR (400 MHz, DMSO-d₆) δ 12.4 (s, 1H), 8.03 (s,1H), 7.64 (s, 1H), 6.90 (s, 1H), 3.85 (s, 3H), 2.27 (s, 3H), 2.08 (s,3H). MS (ES) m/e 272.1 (M+1)⁺.

Intermediate-78: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde

Step-a: Synthesis of N-(4-bromo-3-methoxyphenyl)acetamide

To an ice-cooled solution of 4-bromo-3-methoxyaniline (2.0 g, 9.90 mmol)in DCM (25 mL) was added triethylamine (4.1 mL, 29.7 mmol), afterstirred for 5 min, acetyl chloride (1.05 mL, 14.85 mmol) was added.After completion of reaction, the reaction mixture was quenched with aq.NaHCO₃ solution (up to pH˜8) extracted with DCM (200 mL×2). The combinedorganic layers were washed with water (200 mL), brine (200 mL), driedover sodium sulphate and concentrated. The residue was directly used forthe next step without further purification (2.5 g). ¹H NMR (400 MHz,DMSO-d₆) δ 10.06 (s, 1H), 7.45-7.43 (m, 2H), 7.10 (dd, J₁=2.0 Hz, J₂=8.3Hz, 1H), 3.79 (s, 3H), 2.04 (s, 3H); LC-MS: m/z 244.1 (M+1)⁺.

Step-b: Synthesis of 6-bromo-2-chloro-7-methoxyquinoline-3-carbaldehyde

POCl₃ (7.6 mL, 81.96 mmol) was added drop wise to DMF (2.5 mL, 32.78mmol) at 0° C., after stirred for 5 min, N-(4-bromo-3-methoxyphenyl)acetamide (2.0 g, 8.19 mmol) was added and resulting solution was heatedto 80° C. for 6 h. The reaction mixture was cooled to room temperatureand poured into crushed ice and extracted with EtOAc (200 mL×2) twice.The combined organic layers were washed with water (200 mL), brine (200mL), dried over sodium sulphate and concentrated. The residue wasdirectly used for the next step without further purification (2.0 g). ¹HNMR (400 MHz, DMSO-d₆) δ 10.33 (s, 1H), 8.88 (s, 1H), 8.64 (s, 1H), 7.59(s, 1H), 4.07 (s, 3H); LC-MS: m/z 300 (M+1)⁺.

Step-c: Synthesis of6-bromo-7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde

A suspension of 6-bromo-2-chloro-7-methoxyquinoline-3-carbaldehyde (2.0g, 6.65 mmol) in 70% acetic acid (40 mL) was heated to reflux for 6 h.Upon cooling the reaction mixture to room temperature a solid productwas precipitated out which was filtered and washed with water and driedinvacuo to afford the title compound as brown solid (1.5 g, 80%). ¹H NMR(400 MHz, DMSO-d₆) δ 12.18 (s, 1H), 10.17 (s, 1H), 8.42 (s, 1H), 8.22(s, 1H), 6.93 (s, 1H), 3.94 (s, 3H); LC-MS: m/z 284 (M+1)⁺.

Step-d: Synthesis of6-bromo-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde

To a solution of 6-bromo-7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (9 g, 31.91 mmol) in DMF (80 mL) wereadded potassium carbonate (13.2 g, 95.73 mmol) followed by2-(chloromethyl) pyridine hydrochloride (6.4 g, 35.1 mmol) and stirredat 80° C. for 16 h. After completion of reaction, the reaction mixturewas diluted with water and extracted with EtOAc (400 mL×2). The combinedorganic layers were washed with water (400 mL), brine (300 mL), driedover sodium sulphate and concentrated. The residue was directly used forthe next step without further purification (7.5 g, 63%). ¹H NMR (400MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.51-8.48 (m, 2H), 8.31 (s, 1H), 7.78 (t,J=7.9 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.31-7.28 (m, 1H), 7.13 (s, 1H),5.70 (s, 2H), 3.86 (s, 3H); LC-MS: m/z 373.0 (M)⁺.

Step-e: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde

To a stirred solution of6-bromo-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde(4.0 g, 10.72 mmol) in 1,4-dioxane (40 mL) and H₂O (10 mL) were added3,5-dimethylisoxazoleboronic acid (2.30 g, 16.08 mmol), sodium carbonate(3.41 g, 32.16 mmol) and degassed with nitrogen purging for 20 min. Thentetrakis triphenylphosphine palladium (2.47 g, 2.14 mmol) was added andheated at 100° C. for 8 h. After completion of reaction, the reactionmixture was concentrated and the residue was diluted with EtOAc (200ml), washed with water (200 mL), brine (200 mL), dried over sodiumsulphate and concentrated. The residue was washed with hexane to givetitle compound as yellow solid (3.2 g, 76%). ¹H NMR (400 MHz, DMSO-d₆) δ10.28 (s, 1H), 8.54 (s, 1H), 8.52 (d, J=4.4 Hz, 1H), 7.94 (s, 1H),7.82-7.77 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.33-7.29 (m, 1H), 7.17 (s,1H), 5.72 (s, 2H), 3.81 (s, 3H), 2.27 (s, 3H), 2.08 (s, 3H); LC-MS: m/z390.1 (M+1)⁺.

Intermediate-79: Synthesis of6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-7-methoxyquinolin-2(1H)-one

Step-a: Synthesis of 1-fluoro-2-methoxy-4-nitrobenzene

To a solution of 2-fluoro-5-nitrophenol (5.0 g, 31.84 mmol) in DMF (50mL) was added K₂CO₃ (5.27 g, 38.1 mmol), after stirring at roomtemperature for 15 min was added methyl iodide (3 mL, 47.7 mmol) and thereaction mixture stirred at room temperature for 2 h. Reaction mixturewas poured into ice water, separated solids were filtered, washed thesolid thoroughly with water and vacuum dried to afford an off whitesolid (4.0 g, 73.5%). ¹H NMR (300 MHz, CDCl3): 7.89-7.84 (m, 2H),7.25-7.17 (m, 1H), 3.98 (s, 3H).

Step-b: Synthesis of4-(2-methoxy-4-nitrophenyl)-3,5-dimethyl-4H-1,2,4-triazole

To a solution of 3,5-dimethyl-4H-1,2,4-triazole (0.44 g, 4.49 mmol) inDMF (10 mL) was added NaH (60%)(0.33 g, 8.18 mmol), after stirring atroom temperature for 15 min, was added 1-fluoro-2-methoxy-4-nitrobenzene(0.7 g, 4.09 mmol) and heated at 80° C. for 3 h. The reaction mixturediluted with cold water and extracted with ethyl acetate (100 mL), andwashed with water (50 mL), brine (50 mL), dried over sodium sulphate andconcentrated invacuo to afford yellow oil which was used further stepwithout purification (0.8 g); LC-MS: m/z 249.0 (M+H).

Step-c: Synthesis of4-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-3-methoxyaniline

In a 50 mL round bottom flask, a stirred solution of4-(2-methoxy-4-nitrophenyl)-3,5-dimethyl-4H-1,2,4-triazole (800 mg, 3.22mmol) in Ethanol (20 mL) was added Fe powder (1.26 g, 22.5 mmol) andNH₄Cl (1.2 g, 22.5 mmol) the reaction mixture and heated at 90° C. for 2h. After completion of the reaction, the reaction mixture was dilutedwith ethyl acetate and filtered over celite bed and bed was washed withethyl acetate (2×50 mL). The filtrate was washed sequentially withwater, dried over Na₂SO₄ and concentrated to give title compound as abrown color solid. The crude product was taken to next step without anypurification. (600 mg, crude). LC-MS m/z: 219.1 (M+1)⁺.

Step-d: Synthesis of(E)-N-(4-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-3-methoxyphenyl)-3-ethoxyacrylamide

The process of this step was adopted from step-b of intermediate-2.LC-MS: m/z 317.0 (M+1)⁺.

Step-e: Synthesis of6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-7-methoxyquinolin-2(1H)-one

The process of this step was adopted from intermediate-2 of step-c.LC-MS: m/z 271.1 (M+1)⁺.

The present invention is further exemplified, but not limited, by thefollowing examples that illustrate the preparation of compoundsaccording to the invention.

Example-I: Synthesis of4-(4-chlorobenzyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine(Compound-1)

To a solution of intermediate-1 (0.04 g, 0.15 mmol) in DMF (5 mL) wereadded K₂CO₃ (0.064 g, 0.46 mmol), 4-chloro benzyl bromide (0.038 g, 0.18mmol), and stirred at RT for 24 h. After completion of the reaction, thereaction mixture was diluted with EtOAC (50 mL), washed with water (50mL), brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified on preparative TLC plate to afford the titleproduct as off-white semisolid (0.010 g, 72%). ¹H NMR (400 MHz,DMSO-d₆): δ 7.44-7.39 (m, 4H), 6.53 (s, 1H), 6.39 (s, 1H), 4.55 (s, 2H),4.17 (t, J=4.4 Hz, 2H), 3.55 (s, 3H), 3.40 (s, 2H), 2.19 (s, 3H), 2.02(s, 3H); ES-MS: m/z 385.2 (M+1)⁺.

The below compounds were prepared using the procedure similar to thatfor Compound-1 (Example-I).

Compound No. Structure Characterization data 2

¹H NMR (400 MHz, DMSO-d₆): δ 8.24 (d, J = 2.9 Hz, 1H), 7.88 (d, J = 9.8Hz, 1H), 7.60 (s, 1H), 7.39-7.36 (m, 1H), 7.31-7.29 (m, 1H), 7.22 (s,1H), 6.57 (d, J = 9.3 Hz, 1H), 5.57 (s, 2H), 3.79 (s, 3H), 3.78 (s, 3H),2.24 (s, 3H), 2.05 (s, 3H); LC-MS: m/z 392.1 (M + 1)⁺. 3

1H NMR (300 MHz , CDCl3): 8.63 (m, 1H), 8.03-7.96 (m, 2H) 7.86 (s, 1H),7.52-7.49 (m, 2H), 7.26 (s, 1H), 6.74 (d, J = 9.6 Hz, 1H), 5.83 (s, 2H),3.85 (s, 3H), 2.43 (s, 3H), 2.36 (s, 3H); LC-MS: m/z 362.0 (M + 1)⁺.

Example-II: Synthesis of1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinoxalin-2(1H)-one (Compound-4)

To a stirred solution of6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinoxalin-2(1H)-one (0.117 g,0.4317 mmol) in 2 mL of DMF at 0° C. was added 60% NaH (0.025 g, 1.0869mmol), followed by 4-chlorobenzylbromide (0.098 g, 0.4780 mmol). Thenthe reaction mixture was allowed to stir for 1 h at room temperature.After completion of reaction, the reaction mixture was quenched withmethanol and diluted with ethyl acetate and water. Layers wereseparated, washed with water (50 mL×3), dried over Na₂SO₄ andconcentration. The obtained crude was purified by column chromatographyon silica (2% MeOH in DCM) to give the desired product as an off whitesolid (0.017 g, 11%). ¹HNMR (400 MHz, DMSO-d₆) δ 8.21 (s, 1H), 7.72 (s,1H), 7.43 (s, 4H), 7.01 (s, 1H), 5.56 (s, 2H), 3.81 (s, 3H), 2.25 (s,3H), 2.06 (s, 3H); MS (ES) m/z 396.1 (M+1)⁺.

Example-III: Synthesis of1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one(Compound-5)

To a stirred suspension of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one(0.180 g, 0.629 mmol) in DMF (8 mL) was added potassium t-butoxide(0.140 g, 1.25 mmol). The resulting mixture was refluxed for 2 h, wascooled to 0° C. and 1-(bromo methyl)-4-chlorobenzene (0.194 g, 0.94mmol) and KI (0.005 g, 0.031 mmol) were added. Subsequently, thereaction mixture was refluxed for 12 h, diluted with ethyl acetate andwashed with water (50 mL), dried over Na₂SO₄ and concentration underreduced pressure, followed by chromatography on silica gel (10% EtOAc inhexane) to give the desired product as a white solid (0.020 g, 8%); ¹HNMR (400 MHz DMSO-d₆) δ 7.41-7.34 (m, 4H), 7.07 (s, 1H), 6.64 (s, 1H),5.21 (s, 2H), 3.59 (s, 3H), 2.89 (t, J=7.2 Hz, 2H), 2.20 (t, J=7.1 Hz,2H), 2.21 (s, 3H), 2.03 (s, 3H). MS (ES) m/e 397.3 (M+1)⁺.

Example-IV: Synthesis of4-(1-(4-chlorophenyl)ethyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine(Compound-6)

To a solution of intermediate-1 (0.020 g, 0.076 mmol) in CH₃CN (10 mL)were added Cs₂CO₃ (0.050 g, 0.15 mmol), benzyltriethylammoniumchloride(0.017 mg, 0.007 mmol) followed by1-(4-chlorophenyl)ethylmethanesulfonate (0.018 g, 0.076 mmol), andstirred at 65° C. for 16 h. After completion of reaction, the reactionmixture was diluted with EtOAC (50 mL), washed with water (50 mL), brine(50 mL), dried over sodium sulphate and concentrated. The residue waspurified on preparative HPLC plate to afford the title product as brownsolid (0.003 g, 11%). ¹H NMR (400 MHz, DMSO-d₆): δ 7.50-7.30 (m, 4H),6.53 (s, 1H), 6.52 (s, 1H), 5.22-5.18 (m, 1H), 4.18-3.95 (m, 2H), 3.60(s, 3H), 3.35-3.28 (m, 1H), 3.15-3.05 (m, 1H), 2.20 (s, 3H), 1.98 (s,3H), 1.53 (d, J=6.8 Hz, 3H); LC-MS: m/z 399.2 (M+1)⁺.

The below compounds were prepared according to the above protocol byusing the given starting intermediate and reactant at suitable reactionconditions.

Compound No. Structure Characterization data 7

¹H NMR (400 MHz, CDCl₃): δ 8.68 (s, 1H), 8.56 (d, J = 4.4 Hz, 1H), 7.71(d, J = 7.6 Hz, 1H), 7.34-30 (m, 1H), 6.58 (s, 1H), 6.39 (s, 1H),5.20-5.10 (m, 1H), 4.22-4.17 (m, 2H), 3.63 (s, 3H), 3.40-3.25 (m, 1H),3.18-3.05 (m, 1H), 2.30 (s, 3H), 2.17 (s, 3H), 1.66 (d, J = 6.8 Hz, 3H);LC-MS: m/z 366.2 (M + 1)⁺. 8

¹H NMR (400 MHz, DMSO-d₆): δ 8.74 (s, 1H), 8.56 (s, 2H), 7.91 (d, J =9.3 Hz, 1H), 7.63 (s, 1H), 7.12 (s, 1H), 6.56 (d, J = 9.3 Hz, 1H), 5.74(s, 2H), 3.77 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z 363.2 (M +1)⁺. 9

¹H NMR (400 MHz, DMSO-d₆): δ 8.27 (d, J = 4.4 Hz, 1H), 7.89 (d, J = 9.2Hz 1H), 7.80-7.60 (m, 1H), 7.62 (s, 1H), 7.41-7.39 (m, 1H), 7.03 (s,1H), 6.52 (d, J = 9.2 Hz, 1H), 5.74 (s, 2H), 3.74 (s, 3H), 2.26 (s, 3H),2.07 (s, 3H); LC-MS: m/z 380.2 (M + 1)⁺. 10*

¹H NMR (400 MHz, DMSO-d₆): δ 8.54-8.53 (m, 1H), 7.78- 7.76 (m, 1H),7.33-7.27 (m, 2H), 7.07 (s, 1H), 6.78 (s, 1H), 5.25 (s, 2H), 3.57 (s,3H), 2.92-2.88 (m, 2H), 2.70-2.67 (m, 2H), 2.21 (s, 3H), 2.03 (s, 3H);LC-MS: m/z 364.2 (M + 1)⁺. *Compound-10 was prepared fromintermediate-14 and 2-(chloromethyl)pyridine hydrochloride using theprocedure similar to the one depicted for Compound-6 (Example-IV).

Example-V: Synthesis of 4-((3-chlorophenyl)sulfonyl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine(Compound-11)

To a solution of 3-chlorobenzene-1-sulfonyl chloride (0.052 g, 0.25mmol) in DCM (3 mL) were added pyridine (0.03 mL, 0.38 mmol) followed byintermediate-1 (0.050 g, 0.19 mmol), and stirred at RT for 5 h. Aftercompletion of reaction, the reaction mixture was diluted with EtOAc (50mL), washed with water (50 mL), brine (50 mL), dried over sodiumsulphate and concentrated. The residue was purified on preparative TLCplate to afford the title product (0.020 g, 24%). ¹H NMR (400 MHz,DMSO-d₆): δ 7.83-7.80 (m, 1H), 7.75-7.63 (m, 3H), 7.38 (s, 1H), 6.77 (s,1H), 3.98-3.95 (m, 2H), 3.78-3.74 (m, 2H), 3.74 (s, 3H), 2.23 (s, 3H),2.05 (s, 3H); LC-MS: m/z 435.1 (M+1)⁺.

The below compounds were prepared according to the above protocol byusing the given starting intermediate and reactant at suitable reactionconditions.

Compound No. Structure Characterization data 12

¹H NMR (400 MHz, DMSO-d₆): δ 8.96 (d, J = 2.0 Hz, 1H), 8.89-8.88 (m,1H), 8.20 (d, J = 8.4 Hz, 1H), 7.69-7.65 (m, 1H), 7.40 (s, 1H), 6.76 (s,1H), 4.01-3.99 (m, 2H), 3.81- 3.79 (m, 2H), 3.75 (s, 3H), 2.23 (s, 3H),1.99 (s, 3H); LC-MS: m/z 402.1 (M + 1)⁺. 13

¹H NMR (400 MHz, DMSO-d₆); δ 9.74 (bs, 1H), 7.40 (d, J = 8.3 Hz, 2H),7.29 (d, J = 8.3 Hz, 2H), 6.87 (s, 1H), 6.64 (s, 1H), 5.20 (s, 2H), 4.72(s, 2H), 3.34 (s, 3H), 2.14 (s, 3H), 2.09 (s, 3H); LC-MS: m/z 479.1 (M +1)⁺. 14

¹H NMR (400 MHz, DMSO-d₆): δ 8.45 (d, J = 8.8 Hz, 1H), 8.16 (d, J = 8.3Hz, 2H), 7.94 (s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.33 (s, 1H), 7.19 (d,J = 8.4 Hz, 1H), 3.95 (s, 3H), 2.30 (s, 3H), 2.10 (s, 3H); LC-MS: m/z445.1 (M + 1)⁺. 15

¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 8.3 Hz, 1H), 8.21 (d, J = 8.3Hz, 2H), 7.98 (s, 1H), 7.73 (d, J = 8.3 Hz 2H), 7.50 (s, 1H), 7.41 (d, J= 8.8 Hz, 1H), 3.94 (s, 3H), 2.33 (s, 3H), 2.13 (s, 3H); LC-MS: m/z 409(M + 1)⁺.

Example-VI: Synthesis of2-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)aniline(Compound-16)

Step-i: Synthesis of7-bromo-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine

To a solution of intermediate-1e (2.00 g, 6.99 mmol) in MeOH (10 mL) andH₂O (5 mL) was added KOH (1.17 g, 20.9 mmol) and stirred at refluxtemperature for 2 h. After completion of reaction, the reaction mixturewas diluted with EtOAC (50 mL), washed with water (50 mL), brine (50mL), dried over sodium sulphate and concentrated. The residue was assuch taken forward for the next step without further purification (1.2g, 70%). LC-MS: m/z 246.0 (M+2)²⁺.

Step-ii: Synthesis of7-bromo-6-methoxy-4-(2-nitrobenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

To a solution of 7-bromo-6-methoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine(1.00 g, 4.09 mmol) in DMF (10 mL) were added K₂CO₃ (1.13 g, 8.18 mmol),2-nitro benzylbromide (1.32 g, 6.14 mmol) and stirred at RT for 24 h.After completion of reaction, the reaction mixture was diluted withEtOAC (100 mL), washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The residue was as such taken forwardfor next step without further purification (0.60 g, 37%). ¹H NMR (400MHz, DMSO-d₆): δ 8.09-8.07 (m, 1H), 7.73-7.69 (m, 1H), 7.57-7.48 (m,2H), 6.88 (s, 1H), 6.23 (s, 1H), 4.86 (s, 2H), 4.17-4.15 (m, 2H), 3.53(s, 3H), 3.38-3.36 (m, 2H); LC-MS: m/z 379.1 (M+1)⁺.

Step-iii: Synthesis of2-((7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)aniline

To a ice cooled solution of7-bromo-6-methoxy-4-(2-nitrobenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine(0.5 g, 1.26 mmol) in MeOH (20 mL) were added NiCl₂.6H₂O (0.3 g, 1.26mmol) followed by NaBH₄ (0.23 g, 6.32 mmol) and stirred at the sametemperature for 2 h. After completion of reaction, the reaction mixturewas concentrated, the residue was treated with aq. saturated ammoniumchloride solution and extracted with ethyl acetate (100 mL). The organiclayer was washed with water (50 mL), brine (50 mL), dried over sodiumsulphate and concentrated. The residue was taken forward for next stepwithout further purification (0.2 g, 44%). ¹H NMR (400 MHz, DMSO-d₆): δ7.00-6.90 (m, 2H), 6.88 (s, 1H), 6.75-6.68 (m, 1H), 6.58-6.50 (m, 1H),6.24 (s, 1H), 4.92 (s, 2H), 4.29 (s, 2H), 4.20-4.10 (m, 2H), 3.62 (s,3H), 3.30-3.20 (m, 2H); LC-MS: m/z 349.0 (M+1)⁺.

Step-iv: Synthesis of Compound-16d

To a solution of2-((7-bromo-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl) aniline(0.2 g, 0.27 mmol) in DCM (2 mL) and DIPEA (0.08 mL, 0.54 mmol) wasadded Boc anhydride (0.071 mL, 0.33 mmol) and stirred at RT for 4 h.After completion of reaction, the reaction mixture was diluted withEtOAC (50 mL), washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The residue was taken forward to nextstep without further purification (0.1 g, 32%). ¹H NMR (400 MHz,DMSO-d₆): δ 7.40-7.25 (m, 3H), 7.22-7.18 (m, 1H), 6.87 (s, 1H), 6.20 (s,1H), 4.29 (s, 2H), 4.20-4.15 (m, 2H), 3.53 (s, 3H), 3.35-3.25 (m, 2H),1.36 (s, 18H).

Step-v: Synthesis of tert-butyl(2-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)phenyl)carbamate

To a solution of compound-16d (0.1 g, 1.17 mmol) in toluene (3 mL), EtOH(1.0 mL) and H₂O (1.0 mL) were added 3,5-dimethylisoxazoleboronic acid(0.099 g, 0.35 mmol), sodium carbonate (0.056 g, 0.53 mmol). Theresulting suspension was degassed with nitrogen purging for 20 min. Thentetrakis triphenylphosphine palladium (0.02 g, 0.01 mmol) was added andheated at 100° C. for 16 h. After completion of reaction, the reactionmixture was diluted with EtOAc (50 mL), washed with water (50 mL), brine(50 mL), dried over sodium sulphate and concentrated. The residue wasdirectly used for next step, without further purification 0.1 g (crude).¹H NMR (400 MHz, DMSO-d₆): δ 8.73 (bs, 1H), 7.36-7.12 (m, 4H), 6.53 (s,1H), 6.27 (s, 1H), 4.48 (s, 2H), 4.19 (bs, 2H), 3.50 (s, 3H), 3.39 (bs,2H), 2.19 (s, 3H), 2.06 (s, 3H), 1.49 (s, 9H); LC-MS: m/z 466.3 (M+1)⁺.

Step-vi: Synthesis of2-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)aniline

To an ice-cooled solution of tert-butyl(2-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)phenyl)carbamate(0.1 g, 0.21 mmol) was added methanolic HCl (2 mL) and stirred at RT for3 h. After completion of reaction, the reaction mixture was diluted withEtOAC (50 mL), neutralized with aq. NaHCO₃ solution, washed with water(50 mL), brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified on preparative TLC plate to afford the titleproduct as brown solid (0.020 g, 39%). ¹H NMR (400 MHz, DMSO-d₆+D₂O): δ7.06-6.99 (m, 2H), 6.72-6.70 (m, 1H), 6.60-6.58 (m, 1H), 6.57 (s, 1H),6.42 (s, 1H), 4.32 (s, 2H), 4.19-4.17 (m, 2H), 3.54 (s, 3H), 3.28-3.26(m, 2H), 2.20 (s, 3H), 2.03 (s, 3H); LC-MS: m/z 366.2 (M+1)⁺.

Example-VII: Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one(Compound-17)

To a stirred solution of intermediate-28 (0.10 g, 0.29 mmol) in 1,2-DME(4.0 mL) and H₂O (1.0 mL) were added 3,5-dimethylisoxazoleboronic acid(0.123 g, 0.87 mmol), sodium carbonate (0.077 g, 0.73 mmol) and degassedwith nitrogen purging for 20 min. Then tetrakis triphenylphosphinepalladium (0.017 g, 0.015 mmol) was added and heated at 90° C. for 16 h.After completion of reaction, the reaction mixture was diluted withEtOAc (50 mL), washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The residue was purified by prep. TLCto afford the title compound as a brown solid (0.04 g, 38%). ¹H NMR (400MHz, DMSO-d₆) δ 8.55 (d, J=4.9 Hz, 2H), 7.36 (d, J=4.9 Hz, 2H), 6.96 (s,1H), 6.66 (s, 1H), 5.27 (s, 2H), 4.80 (s, 2H), 3.58 (s, 3H), 2.22 (s,3H), 2.04 (s, 3H); LC-MS: m/z 366.1 (M+1)⁺.

The below compounds were prepared by procedure similar to the onedescribed in Example-VII with appropriate variations in reactants,quantities of reagents and reaction conditions. The physiochemicalcharacteristics of the compounds are summarized herein below table.

Compound No. Structure Characterization Data 18

¹H NMR (400 MHz, DMSO-d₆) δ 7.45-7.38 (m, 4H), 6.93 (s, 1H), 6.75 (s,1H), 5.23 (s, 2H), 4.77 (s, 2H), 3.62 (s, 3H), 2.21 (s, 3H), 2.03 (s,3H); ES-MS: m/z 399.1 (M + 1)⁺. 19 & 20

Compound 19 (Isomer-1): ¹H NMR (400 MHz, CDCl₃): δ 8.63 (dd, J = 4.4 &2.4 Hz, 2H), 7.30 (d, J = 4.8 Hz, 2H), 6.79 (s, 1H), 6.40-6.30 (m, 1H),6.14 (s, 1H), 4.75-4.60 (m, 2H), 3.37 (s, 3H), 2.26 (s, 3H), 2.11 (s,3H), 1.88 (d, J = 7.2 Hz, 3H); LC-MS: m/z 380.2 (M + 1)⁺. Compound 20(Isomer-2): ¹H NMR (400 MHz, CDCl₃): δ 8.64 (d, J = 5.6 Hz, 2H), 7.30(d, J = 4.8 Hz, 2H), 6.79 (s, 1H), 6.42-6.30 (m, 1H), 6.14 (s, 1H),4.80-4.60 (m, 2H), 3.37 (s, 3H), 2.26 (s, 3H), 2.12 (s, 3H), 1.88 (d, J= 7.2 Hz, 3H); LC- MS: m/z 380.2 (M + 1)⁺. 21

¹H NMR (400 MHz, DMSO-d₆) δ 8.66 (s, 1H), 8.57 (d, J = 4.4 Hz, 1H), 7.66(d, J = 7.6 Hz, 1H), 7.33-7.30 (m, 1H), 6.78 (s, 1H), 6.47 (s, 1H), 5.22(s, 2H), 4.72 (s, 2H), 3.60 (s, 3H), 2.27 (s, 3H), 2.13 (s, 3H); LC-MS:m/z 366.2 (M + 1)⁺. 22

¹H NMR (400 MHz, CDCl₃) δ 8.59 (d, J = 4.8 Hz, 1H), 8.69 (td, J = 8.0 &2.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.24-7.22 (m, 1H), 6.95 (s, 1H),6.75 (s, 1H), 5.30 (s, 2H), 4.71 (s, 2H), 3.66 (s, 3H), 2.27 (s, 3H),2.13 (s, 3H); LC-MS: m/z 366.1 (M + 1)⁺. 23

¹H NMR (400 MHz, CDCl₃) δ 6.79 (s, 1H), 6.60 (s, 1H), 4.60 (s, 2H), 4.00(dd, J = 4.2 & 2.4 Hz, 2H), 3.90 (d, J = 7.2 Hz, 2H), 3.77 (s, 3H), 3.36(t, J = 11.2 Hz, 2H), 2.31 (s, 3H), 2.18 (s, 3H), 2.08-2.00 (m, 1H),1.64-1.60 (m, 2H), 1.58- 1.40 (m, 2H); LC-MS: m/z 373.2 (M + 1)⁺. 24 &25

Compound 24 (Isomer-1): ¹H NMR (400 MHz, CDCl₃): δ 8.69 (s, 1H), 8.58(d, J = 4.4 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.35-7.31 (m, 1H), 6.78(s, 1H), 6.41 (q, J = 7.2 Hz, 1H), 6.25 (s, 1H), 4.72-4.62 (m, 2H), 3.40(s, 3H), 2.26 (s, 3H), 2.12 (s, 3H), 1.93 (d, J = 6.8 Hz, 3H). LC-MS:m/z 380.2 (M + 1)⁺. Compound 25 (Isomer-2): ¹H NMR (400 MHz, CDCl₃): δ8.70 (s, 1H), 8.58 (d, J = 4.4 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H),7.35-7.32 (m, 1H), 6.78 (s, 1H), 6.41 (q, J = 7.2 Hz, 1H), 6.25 (s, 1H),4.72-4.62 (m, 2H), 3.40 (s, 3H), 2.26 (s, 3H), 2.11 (s, 3H), 1.93 (d, J= 6.8 Hz, 3H); LC-MS: m/z 380.2 (M + 1)⁺. 26

¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 2.4 Hz, 1H), 7.57 (dd, J = 8.8 &2.4 Hz, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 6.57 (s, 1H), 5.12 (s, 2H),4.69 (s, 2H), 3.92 (s, 3H), 3.65 (s, 3H), 2.27 (s, 3H), 2.13 (s, 3H);LC-MS: m/z 396.1 (M + 1)⁺. 27

¹H NMR (400 MHz, CDCl₃): δ 8.86 (d, J = 1.6 Hz, 1H), 7.97 (dd, J = 8.0 &2.0 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 6.81 (s, 1H), 6.78 (s, 1H), 5.33(s, 2H), 4.70 (s, 2H), 3.67 (s, 3H), 2.27 (s, 3H), 2.13 (s, 3H); LC-MS:m/z 391.2 (M + 1)⁺. 28

¹H NMR (400 MHz, CDCl₃) δ 8.54 (d, J = 2.0 Hz, 1H), 7.67 (dd, J = 8.0,2.4 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.96 (s, 1H), 6.75 (s, 1H), 5.26(s, 2H), 4.69 (s, 2H), 3.69 (s, 3H), 2.27 (s, 3H), 2.13 (s, 3H); LC-MS:m/z 400.2 (M + 1)⁺. 29

¹H NMR (400 MHz, CDCl₃) δ 8.43 (d, J = 2.0 Hz, 1H), 7.45- 7.26 (m, 2H),7.00 (s, 1H), 6.75 (s, 1H), 5.27 (s, 2H), 4.69 (s, 2H), 3.69 (s, 3H),2.27 (s, 3H), 2.13 (s, 3H); LC-MS: m/z 384.2 (M + 1)⁺. 30

¹H NMR (400 MHz, CDCl₃) δ 8.25 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 8.8 Hz,1H), 7.19 (dd, J = 8.8 & 2.0 Hz, 1H), 7.10 (s, 1H), 6.73 (s, 1H), 5.23(s, 2H), 4.68 (s, 2H), 3.70 (s, 3H), 3.58 (s, 3H), 2.27 (s, 3H), 2.13(s, 3H); LC-MS: m/z 396.2 (M + 1)⁺. 31

¹H NMR (400 MHz, CDCl₃) δ 8.60 (bs, 1H), 7.82-7.79 (m, 1H), 7.62 (d, J =8.4 Hz, 1H), 7.34-7.31 (m, 1H), 6.92 (s, 1H), 6.63 (s, 1H), 6.24-6.22(m, 1H), 4.67 (s, 2H), 3.43 (s, 3H), 2.21 (s, 3H), 1.97 (s, 3H), 1.84(d, J = 6.9 Hz, 3H); LC-MS: m/z 380.2 (M + 1)⁺. 32

¹H NMR (400 MHz, CDCl₃): δ 8.58 (s, 1H), 7.56 (d, J = 7.4 Hz, 1H), 7.17(d, J = 7.6 Hz, 1H), 6.77 (s, 1H), 6.51 (s, 1H), 5.17 (s, 2H), 4.70 (s,2H), 3.61 (s, 3H), 2.55 (s, 3H), 2.26 (s, 3H), 2.12 (s, 3H); ES-MS: m/z380.2 (M + 1)⁺. 33 & 34

Compound 33 (Isomer-1): ¹H NMR (400 MHz, CDCl₃): δ 7.37-7.30 (m, 4H),6.76 (s, 1H), 6.45-6.35 (m, 1H), 6.27 (s, 1H), 4.72-4.60 (m, 2H), 3.38(s, 3H), 2.25 (s, 3H), 2.12 (s, 3H), 1.84 (d, J = 7.4 Hz, 3H); LC-MS:m/z 413.0 (M + 1)⁺. Compound 34 (Isomer-2): ¹H NMR (400 MHz, CDCl₃): δ7.31-7.27 (m, 4H), 6.69 (s, 1H), 6.35-6.28 (m, 1H), 6.20 (s, 1H),4.65-4.54 (m, 2H), 3.32 (s, 3H), 2.19 (s, 3H), 2.05 (s, 3H), 1.78 (d, J= 6.9 Hz, 3H); LC-MS: m/z 413.0 (M + 1)⁺. 35

¹H NMR (400 MHz, DMSO-d₆): δ 8.57 (d, J = 3.4 Hz, 1H), 7.61 (t, J = 6.9Hz, 1H), 7.26 (s, 1H), 7.21-7.14 (m, 1H), 6.89 (s, 1H), 6.74 (s, 1H),4.60 (s, 2H), 4.37 (t, J = 7.3 Hz, 2H), 3.79 (s, 3H), 3.20 (t, J = 7.6Hz, 2H), 2.30 (s, 3H), 2.15 (s, 3H); LC-MS: m/z 380.1 (M + 1)⁺. 36

¹H NMR (400 MHz, DMSO-d₆): δ 8.64 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 3.5Hz, 1H), 7.92 (d, J = 9.3 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.64 (s,1H), 7.36 (dd, J = 4.9 & 3.0 Hz, 1H), 7.01 (s, 1H), 6.60 (d, J = 9.3 Hz,1H), 5.63 (s, 2H), 3.78 (s, 3H), 2.24 (s, 3H), 2.05 (s, 3H); LC-MS: m/z362.2 (M + 1)⁺. 37

¹H NMR (400 MHz, DMSO-d₆): δ 8.57 (d, J = 2.0 Hz, 1H), 7.90-7.78 (m,2H), 7.62 (s, 1H), 7.41 (d, J = 7.3 Hz, 1H), 7.07 (s, 1H), 6.57 (d, J =9.3 Hz, 1H), 5.65 (s, 2H), 3.76 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H);LC-MS: m/z 396.1 (M + 1)⁺. 38

¹H NMR (400 MHz, DMSO-d₆): δ 7.83 (d, J = 9.0 Hz, 1H), 7.61 (s, 1H),7.07 (s, 1H), 6.47 (d, J = 9.7 Hz, 1H), 4.43 (t, J = 7.3 Hz, 2H), 3.94(s, 3H), 3.58 (t, J = 4.4 Hz, 4H), 2.61- 2.54 (m, 6H), 2.49 (s, 3H),2.09 (s, 3H); LC-MS: m/z 384.2 (M + 1)⁺. 39

¹H NMR (400 MHz, DMSO-d₆): δ 7.92-7.90 (m, 1H), 7.78- 7.77 (m, 1H),7.71-7.70 (m, 1H), 7.63 (s, 1H), 7.36 (s, 1H), 6.57 (d, J = 9.7 Hz, 1H),5.85 (s, 2H), 3.86 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z 368.1(M + 1)⁺. 40

¹H NMR (400 MHz, DMSO-d₆): δ 8.57-8.56 (m, 1H), 8.19- 8.14 (m, 1H), 7.78(dt, J = 7.8, 1.9 Hz, 1H), 7.73 (s, 1H), 7.49 (d, J = 8.0 Hz, 1H),7.31-7.29 (m, 1H), 7.18 (s, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.49-6.44 (m,1H), 3.88 (s, 3H), 2.32 (s, 3H), 2.08 (s, 3H), 1.67 (d, J = 6.4 Hz, 3H);LC-MS: m/z 376.2 (M + 1)⁺. 41

¹H NMR (400 MHz, DMSO-d₆): δ 8.76 (s, 1H), 8.50-8.48 (m, 1H), 8.16 (d, J= 8.8 Hz, 1H), 7.94-7.91 (m, 1H), 7.73 (s, 1H), 7.41-7.38 (m, 1H), 7.23(s, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.51-6.46 (m, 1H), 3.89 (s, 3H), 2.27(s, 3H), 2.08 (s, 3H), 1.69 (d, J = 6.0 Hz, 3H); LC-MS: m/z 376.2 (M +1)⁺. 42

¹H NMR (400 MHz, DMSO-d₆): δ 8.53-8.50 (m, 1H), 8.13 (d, J = 8.8 Hz,1H), 7.76-7.70 (m, 1H), 7.72 (s, 1H), 7.39- 7.35 (m, 1H), 7.30 (s, 1H),7.28-7.22 (m, 1H), 6.82 (d, J = 8.8 Hz, 1H), 4.79 (t, J = 6.8 Hz, 2H),3.41 (s, 3H), 3.27 (t, J = 6.8 Hz, 2H), 2.29 (s, 3H), 2.08 (s, 3H);LC-MS: m/z 376.2 (M + 1)⁺. 43

¹H NMR (400 MHz, DMSO-d₆): δ 8.76-8.73 (m, 2H), 7.90 (d, J = 9.2 Hz,1H), 7.62 (s, 1H), 7.43-7.40 (m, 1H), 6.90 (s, 1H), 6.54 (d, J = 9.2 Hz,1H), 5.75 (s, 2H), 3.69 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z363.2 (M + 1)⁺. 44

¹H NMR (400 MHz, DMSO-d₆): δ 9.10 (d, J = 2.0 Hz, 1H), 8.75 (d, J = 7.2Hz, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.65 (s, 1H), 7.45-7.43 (m, 1H), 6.97(s, 1H), 6.57 (d, J = 9.4 Hz, 1H), 5.68 (s, 2H), 3.74 (s, 3H), 2.26 (s,3H), 2.06 (s, 3H); LC-MS: m/z 363.2 (M + 1)⁺. 45

¹H NMR (400 MHz, DMSO-d₆): δ 8.53 (d, J = 3.0 Hz, 1H), 7.90 (d, J = 9.2Hz, 1H), 7.74-7.69 (m, 1H), 7.62 (s, 1H), 7.46-7.43 (m, 1H), 7.11 (s,1H), 6.57 (d, J = 9.2 Hz, 1H), 5.65 (s, 2H), 3.77 (s, 3H), 2.25 (s, 3H),2.06 (s, 3H); LC-MS: m/z 380.2 (M + 1)⁺. 46

¹H NMR (400 MHz, DMSO-d₆): δ 8.52 (d, J = 4.4 Hz, 1H), 7.90 (d, J = 9.6Hz, 1H), 7.79-7.75 (m, 1H), 7.62 (s, 1H), 7.33-7.28 (m, 2H), 7.12 (s,1H), 6.58 (d, J = 9.6 Hz, 1H), 5.65 (s, 2H), 3.74 (s, 3H), 2.24 (s, 3H),2.05 (s, 3H). MS (ES) m/z 362.3 (M + 1)⁺. 47

¹H NMR (CDCl₃, 400 MHz): δ 8.83 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.65(d, J = 9.2 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.26 (s, 1H), 7.15 (s,1H), 6.67 (d, J = 9.6 Hz, 1H), 5.73 (bs, 2H), 3.80 (s, 3H), 2.26 (s,3H), 2.11 (s, 3H); LC-MS: m/z 430.1 (M + 1)⁺, 48

¹H NMR (400 MHz, DMSO-d₆) δ 8.53-8.52 (m, 1H), 7.77- 7.73 (m, 1H),7.37-7.25 (m, 2H), 7.11 (s, 1H), 6.81 (s, 1H), 5.29 (s, 2H), 3.59 (s,3H), 2.59 (s, 2H), 2.22 (s, 3H), 2.04 (s, 3H), 1.25 (s, 6H); LC-MS: m/z392.2 (M + 1)⁺. 49

¹H NMR (400 MHz, DMSO-d₆): δ 8.62 (s, 1H), 8.56 (d, J = 3.9 Hz, 1H),7.61 (d, J = 7.9 Hz, 1H), 7.32-7.29 (m, 1H), 6.75 (s, 1H), 6.42 (s, 1H),5.18 (s, 2H), 3.59 (s, 3H), 2.27 (s, 3H), 2.13 (s, 3H), 1.58 (s, 6H);LC-MS: m/z 394.2 (M + 1)⁺. 50

¹H NMR (400 MHz, CDCl₃): δ 8.58 (s, 1H), 7.64-7.61 (m, 1H), 7.54 (s,1H), 7.34-7.32 (m, 1H), 7.20-7.17 (m, 3H), 5.71 (s, 2H), 3.77 (s, 3H),2.31 (s, 3H), 2.31 (s, 3H), 2.26 (s, 3H); LC-MS: m/z 376.2 (M + 1)⁺. 51

¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 4.4 Hz, 1H), 7.79-7.75 (m,1H), 6.55 (s, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.35-7.25 (m, 1H), 6.94 (s,1H), 5.41 (s, 2H), 3.74 (s, 3H), 2.22 (s, 3H), 2.02 (s, 3H), 1.42 (s,6H); LC-MS: m/z 406.2 (M + 1)⁺. 52

¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 7.8 Hz, 1H), 7.66-7.62 (m,1H), 7.30-7.18 (m, 2H), 6.84 (s, 1H), 6.78 (s, 1H), 5.30 (s, 2H), 3.63(s, 3H), 2.79 (s, 2H), 2.26 (s, 3H), 2.12 (s, 3H), 1.27 (s, 6H); LC-MS:m/z 392.2 (M + 1)⁺. 53

¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 3.9 Hz, 1H), 7.78-7.74 (m,1H), 7.59 (s, 1H), 7.36-7.27 (m, 2H), 7.10 (s, 1H), 6.50 (s, 1H), 5.63(s, 2H), 3.73 (s, 3H), 2.44 (s, 3H), 2.25 (s, 3H), 2.05 (s, 3H); LC-MS:m/z 376.2 (M + 1)⁺. 54

¹H NMR (400 MHz, CDCl₃) δ 8.59 (d, J = 4.4 Hz, 1H), 7.67 (dt J = 8.0,0.8 Hz, 1H), 7.54 (d, J = 0.8 Hz, 1H), 7.42-7.38 (m, 2H), 7.25-7.20 (m,1H), 7.08 (s, 1H), 5.71 (bs, 2H), 3.85 (s, 3H), 2.28 (s, 3H), 2.14 (s,3H); LC-MS: m/z 430.2 (M + 1)⁺. 55

¹H NMR (400 MHz, DMSO-d₆) δ 8.54-8.52 (m, 1H), 7.94 (s, 1H), 7.77 (dt, J= 7.8, 2.0 Hz, 1H), 7.31-7.28 (m, 2H), 7.13 (s, 1H), 6.27 (s, 1H), 5.63(s, 2H), 3.74 (s, 3H), 2.32-2.29 (m, 1H), 2.27 (s, 3H), 2.08 (s, 3H),1.06-1.01 (m, 2H), 0.81- 0.77 (m, 2H); LC-MS: m/z 402.2 (M + 1)⁺. 56

¹HNMR 400 MHz (DMSO-d₆) δ 7.91 (d, J = 9.2 Hz, 1H), 7.63 (s, 1H),7.40-7.36 (m, 4H), 6.96 (s, 1H), 6.60 (d, J = 9.2 Hz, 1H), 5.58 (s, 2H),3.77 (s, 3H), 2.24 (s, 3H), 2.05 (s, 3H). MS (ES) m/e 395.3 (M + 1)⁺. 57

¹H NMR (400 MHz DMSO-d₆): δ 8.41 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 8.8Hz, 1H), 8.01-7.98 (m, 2H), 7.81-7.77 (m, 2H), 7.69 (d, J = 8.3 Hz, 1H),7.62 (t, J = 7.8 Hz, 1H), 7.27 (s, 1H), 7.08 (d, J = 8.8 Hz, 1H), 5.79(s, 2H), 3.89 (s, 3H), 2.30 (s, 3H), 2.10 (s, 3H); LC-MS: m/z 412.2 (M +1)⁺. 58

¹H NMR (400 MHz, DMSO-d₆): δ 8.58 (d, J = 2.4 Hz, 1H), 7.91 (dd, J1 =2.4 Hz, J2 = 8.8 Hz, 1H), 7.79 (s, 1H), 7.53 (s, 1H), 7.39 (d, J = 8.8Hz, 1H), 7.05 (s, 1H), 5.67 (s, 2H), 3.75 (s, 3H), 2.25 (s, 3H), 2.15(s, 3H), 2.06 (s, 3H); LC-MS: m/z 410.2 (M + 1)⁺. 59

¹H NMR (400 MHz, CDCl₃): δ 7.52 (s, 1H), 7.35-7.23 (m, 5H), 6.72 (s,1H), 4.50 (t, J = 7.8 Hz, 2H), 3.88 (s, 3H), 3.07 (t, J = 7.9 Hz, 2H),2.27 (s, 3H), 2.26 (s, 3H), 2.16 (s, 3H); LC-MS: m/z 423.1 (M + 1)⁺. 60*

¹H NMR (400 MHz, DMSO-d₆) δ 8.34 (bs, 1H), 6.93 (s, 1H), 6.89 (s, 1H),4.63 (s, 2H), 3.94 (d, J = 7.7 Hz, 2H), 3.80 (s, 3H), 3.14 (d, J = 11.7Hz, 2H), 2.75-2.60 (m, 2H), 2.33 (s, 3H), 2.08 (s, 3H), 2.05-1.80 (m,1H), 1.75-1.55 (m, 2H), 1.42-1.28 (m, 2H); LC-MS: m/z 372.2 (M + 1)⁺; 61*

¹H NMR (300 MHz, CD₃OD): δ 8.53 (d, J = 5.1 Hz, 1H), 7.95 (d J = 9.6 Hz,1H), 7.82-7.74 (m, 2H), 7.64 (s, 1H), 7.85 (d, J = 2.7 Hz, 1H),7.34-7.25 (m, 2H), 7.04 (s, 1H), 6.6 (d, J = 9.3 Hz, 1H), 6.56 (d, J =9.6 Hz, 1H), 5.74 (s, 2H), 3.78 (s, 3H); LC-MS: m/z 360.10 (M + 1)⁺. 62

¹H NMR (300 MHz, CDCl₃): δ 8.82 (s, 1H), 7.76-7.68 (m, 2H), 7.41-7.38(m, 1H), 7.34-7.30 (m, 1H), 7.15 (s, 1H), 6.71 (d, J = 6.6 Hz, 2H), 5.78(s, 2H), 3.80 (s, 3H), 2.24 (s, 3H), 1.55-1.50 (m, 1H), 1.02-0.96 (m,2H), 0.88-0.81 (m, 2H). LCMS (ESI, m/z): 388.0 (M + 1)⁺. 63

¹H NMR (CDCl₃, 300 MHz): δ 8.58 (d, J = 4.2 Hz, 1H), 8.31 (s, 1H), 7.65(d, J = 9.3 Hz, 1H), 7.59 (dd, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.35 (s,1H), 7.31 (d, J = 7.8 Hz, 1H), 7.26-7.20 (m, 2H), 6.68 (d, J = 9.3 Hz,1H), 5.70 (bs, 2H), 3.83 (s, 3H), 2.45 (s, 3H). LC-MS: m/z 348.1 (M +1)⁺. 64

¹H NMR (CDCl₃, 300 MHz): δ 8.85-8.78 (m, 1H), 8.46 (s, 1H), 7.97 (dt, J= 8.1 & 1.5 Hz, 1H), 7.75 (d, J = 9.3 Hz, 1H), 7.56 (t, J = 6.0 Hz, 1H),7.60 (d, J = 7.8 Hz, 1H), 7.48 (s, 1H), 6.99 (s, 1H), 6.74 (d, J = 9.3Hz, 1H), 5.98 (s, 2H), 3.83 (s, 3H), 2.32 (s, 3H); LC-MS: m/z 348.2 (M +1)⁺. 65

¹H NMR (400 MHz, DMSO-d₆): δ 12.30-12.10 (bs, 1H), 7.44-7.39 (m, 4H),6.75 (s, 1H), 6.68 (s, 1H), 5.21 (s, 2H), 4.74 (s, 2H), 3.56 (s, 3H),1.98 (s, 6H); LC-MS: m/z 398.2 (M + 1)⁺. 66

¹H NMR (400 MHz, DMSO-d₆): δ 12.19 (s, 1H), 8.53 (d, J = 3.4, 1H), 7.89(d, J = 9.8 Hz, 1H), 7.76 (t, J = 7.8 Hz, 1H), 7.47 (s, 1H), 7.30 (d, J= 7.4 Hz, 2H), 7.05 (s, 1H), 6.54 (d, J = 9.3 Hz, 1H), 5.63 (s, 2H),3.69 (s, 3H), 2.00 (s, 6H); LC- MS: m/z 361.2 (M + 1)⁺. 67

¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 9.3Hz, 1H), 7.74 (d, J = 6.9 Hz, 1H), 7.65 (s, 1H), 7.49 (d, J = 8.4 Hz,1H), 7.00 (s, 1H), 6.60 (d, J = 9.2 Hz, 1H), 5.63 (s, 2H), 3.81 (s, 3H),2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z 396.2 (M + 1)⁺. 68

¹H NMR (400 MHz, DMSO-d₆): δ 8.53 (d, J = 4.4 Hz, 1H), 7.78-7.74 (m,1H), 7.72 (s, 1H), 7.58 (s, 1H), 7.31-7.27 (m, 2H), 7.10 (s, 1H), 5.66(s, 2H), 3.72 (s, 3H), 2.86-2.81 (m, 1H), 2.24 (s, 3H), 2.05 (s, 3H),1.90-1.72 (m, 6H), 1.41-1.28 (m, 4H); LC-MS: m/z 444.3 (M + 1)⁺. 69

¹H NMR (400 MHz, DMSO-d₆): δ 8.63 (s, 1H), 8.47 (bs, 1H), 7.73 (s, 1H),7.68-7.66 (m, 1H), 7.60 (s, 1H), 7.38-7.36 (m, 1H), 7.0 (s, 1H), 5.66(s, 2H), 3.77 (s, 3H), 2.85-2.62 (m, 1H), 2.24 (s, 3H), 2.05 (s, 3H),1.91-1.72 (m, 6H), 1.45-1.29 (m, 4H); LC-MS: m/z 444.3 (M + 1)⁺.NOTE: Synthesis of Compound 60 comprises deprotection reaction accordingto the procedure depicted in below step:

Deprotection (for Compound-60)7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-(piperidin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

To an ice-cooled solution of tert-butyl4-((7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)methyl)piperidine-1-carboxylate(0.20 g, 0.42 mmol) in DCM (10 mL) was add TFA (6.0 mL, 39.20 mmol) andstirred at same temperature for 1 h. Reaction mixture was concentratedin vacuo, and residue was triturated with hexane to afford a whitesolid. The solid was suspended in DCM (5 mL) and at 0° C. was addedsaturated aq. NaHCO₃ solution (1.0 mL), stirred for 1 h at sametemperature. The organic layer separated, dried over Na₂SO₄,concentrated in vacuo to afford the title product as an off white semisolid (0.01 g, 6%).

Similarly synthesis Compound-61 comprises debenzylation reactionaccording to the procedure depicted hereinafter.

Debenzylation (for Compound-61)N-(4-(6-hydroxypyridin-3-yl)-5-methoxy-2-methylphenyl)-N-(pyridin-2-ylmethyl)acetamide

In a 25 mL single neck round bottom flask, a stirred solution6-(6-(benzyloxy)pyridin-3-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(0.040 g, 0.08 mmol) in MeOH (3 mL) was treated with Pd/C (10%, 0.050 g)at RT under nitrogen atmosphere. The suspension was hydrogenated(balloon pressure) at RT for 30 min. Upon completion of reaction (TLC),the reaction mixture was filtered and filtrate was concentrated underreduced pressure to give title compound as an off white solid (0.010 g,30.3%).

Example-VIII: Synthesis of7-(3,5-dimethylisoxazol-4-yl)-4-((6-hydroxypyridin-3-yl)methyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(Compound-70)

A solution of compound-26 (0.04 g, 0.10 mmol) in 33% HBr in AcOH (3.0mL) was heated at 100° C. in a sealed tube for 6 h. After completion ofreaction, the reaction was quenched by the addition of water (10 mL)followed by saturated aq. sodium bicarbonate solution (20 mL) andextracted with 10% MeOH:DCM (100 mL). The organic layer was washed withwater (50 mL), brine (50 mL), dried over sodium sulphate andconcentrated under reduced pressure. The residue was purified bypreparative TLC to isolate the title product as a brown solid (5 mg,13%). ¹H NMR (400 MHz, CDCl₃): δ 7.52 (m, 1H), 7.32 (s, 1H), 6.79 (s,1H), 6.60 (d, J=9.6 Hz, 1H), 6.49 (s, 1H), 4.94 (s, 2H), 4.66 (s, 2H),3.67 (s, 3H), 2.29 (s, 3H), 2.15 (s, 3H); LC-MS: m/z 382.1 (M+1)⁺.

Example-IX: Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-(2-methoxyethoxy)-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one(Compound-71)

Step-(i): Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-hydroxy-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

To an ice cooled solution of compound-17 (0.10 g, 0.27 mmol) in DCM (4.0mL) was added BBr₃ (1.0M in DCM, 1 mL) and stirred at 100° C. for 16 h.After completion of reaction, the reaction was quenched by the additionof aq. sodium bicarbonate solution and extracted with DCM (50 mL). Theorganic layer was washed with water (50 mL), brine (50 mL), dried oversodium sulphate and concentrated. The residue was purified by prep. TLCto afford the title compound as off-white solid (0.080 g, 84%). ¹H NMR(400 MHz, CDCl₃) δ 8.46-8.44 (m, 2H), 7.20-7.19 (m, 2H), 6.77 (s, 1H),6.39 (s, 1H), 5.14 (s, 2H), 4.74 (s, 2H), 2.32 (s, 3H), 2.18 (s, 3H);ES-MS: m/z 350.2 (M−1)⁻.

Step-(ii): Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-(2-methoxyethoxy)-4-(pyridin-4-ylmethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

To a solution of compound-71a (0.08 g, 0.23 mmol) in DMF (3.0 mL) wereadded K₂CO₃ (0.095 g, 0.069 mmol) followed by 1-bromo-2-methoxyethane(0.064 g, 0.46 mmol) and stirred at 50° C. for 16 h. After completion ofreaction, the reaction was diluted with water (10 mL) and extracted withEtOAc (50 mL). The organic layer was washed with water (50 mL), brine(50 mL), dried over sodium sulphate and concentrated. The residue waspurified by prep. TLC to afford the title compound as white solid (0.010g, 11%). ¹H NMR (400 MHz, CDCl₃) δ 8.61 (d, J=5.4 Hz, 2H), 7.22 (d,J=5.8 Hz, 2H), 6.80 (s, 1H), 6.44 (s, 1H), 5.17 (s, 2H), 4.75 (s, 2H),3.78 (t, J=4.6 Hz, 2H), 3.50 (t, J=4.4 Hz, 2H), 3.27 (s, 3H), 2.29 (s,3H), 2.16 (s, 3H); LC-MS: m/z 410.2 (M+1)⁺.

The below compounds were prepared by procedure similar to any or both ofthe steps depicted in Example-IX with appropriate variations inreactants, quantities of reagents and reaction conditions. Thephysiochemical characteristics of the compounds are summarized hereinbelow table.

Compound No. Structure Characterization Data 72

¹H NMR (300 MHz, CDCl₃): δ 9.8 (bs, 1H), 8.16-814 (m, 1H), 7.71-7.65 (m,2H), 7.32 (s, 1H), 7.17-7.14 (m, 2H), 6.94 (s, 1H), 6.55 (d, J = 9.0 Hz,1H), 5.65 (s, 2H), 3.34 (s, 3H), 3.20 (s, 3H); LC-MS: m/z 348.1 (M +1)⁺. 73

¹H NMR (400 MHz, DMSO-d₆): δ 10.45 (s, 1H), 8.59 (d, J = 2.4 Hz, 1H),7.90 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.87 (d, J = 9.8 Hz, 1H), 7.56(s, 1H), 7.24 (d, J = 8.3 Hz, 1H), 6.81 (s, 1H), 6.50 (d, J = 9.8 Hz,1H), 5.48 (s, 2H), 2.25 (s, 3H), 2.09 (s, 3H); LC-MS: m/z 382.1 (M +1)⁺. 74

¹H NMR (300 MHz, CDCl₃): δ 8.58 (d, J = 4.2 Hz, 1H), 7.69- 7.63 (m, 2H),7.45 (s, 1H), 7.42-7.41 (m, 1H), 7.31 (s, 1H), 7.25-7.22 (m, 1H), 6.74(d, J = 9.3 Hz, 1H), 5.66 (s, 2H), 4.41- 4.33 (m, 2H), 2.27 (s, 3H),2.13 (s, 3H); LC-MS: m/z 430.1 (M + 1)⁺. 75

¹H NMR (300 MHz, CDCl₃): δ 8.57 (d, J = 4.8 Hz, 1H), 7.67- 7.61 (m, 2H),7.34 (d, J = 7.8 Hz, 1H), 7.23-7.20 (m, 3H), 6.69 (d, J = 9.3 Hz, 1H),5.67 (s, 2H), 4.07 (t, J = 5.4 Hz, 2H), 3.74- 3.64 (m, 4H), 2.68 (t, J =6.3 Hz, 2H), 2.45-2.42 (m, 4H), 2.27 (s, 3H), 2.14 (s, 3H); LC-MS: m/z461.2 (M + 1)⁺. 76

¹H NMR (300 MHz, CDCl₃): δ 8.57 (d, J = 4.8 Hz, 1H), 7.67- 7.60 (m, 2H),7.34 (d, J = 7.8 Hz, 1H), 7.23-7.18 (m, 3H), 6.69 (d, J = 9.3 Hz, 1H),5.67 (s, 2H), 4.04 (t, J = 5.7 Hz, 2H), 2.62 (t, J = 5.7 Hz, 2H), 2.27(s, 3H), 2.23 (s, 6H), 2.13 (s, 3H); LC-MS: m/z 419.3 (M + 1)⁺.  77*

¹H NMR (CD₃OD, 300 MHz): δ 8.83 (s, 1H), 8.48-8.44 (m, 1H), 8.03 (d, J =9.6 Hz, 1 H), 7.94 (bs, 1H), 7.76 (d, J = 7.6 Hz, 1 H), 7.65 (s, 1H),7.21 (s, 1H), 6.66 (d, J = 9.6 Hz, 1 H), 6.00 (s, 2H), 4.05 (s, 2H),3.73-3.66 (m, 1H) 3.39-3.34 (m, 2H), 3.01-2.95 (m, 2H), 2.29 (s, 3H),2.12 (s, 3H), 1.92-1.88 (m, 2H), 1.52-1.49 (m, 2H); LC-MS: m/z 445.05(M + 1)⁺. 78

¹HNMR (300 MHz, CDCl₃): δ 8.57 (d, J = 4.2 Hz, 1H), 7.67- 7.60 (m, 2H),7.34 (d, J = 8.1 Hz, 1H), 7.26-7.17 (m, 3H), 6.68 (d, J = 9.6 Hz, 1H),5.68 (s, 2H), 3.93 (t, J = 6.9 Hz, 2H), 2.26 (s, 3H), 2.12 (s, 3H), 1.68(t, J = 6.9 Hz, 2H), 1.39-1.32 (m, 2H), 0.90 (t, J = 6.9 Hz, 3H); LC-MS:m/z 404.1 (M + 1)⁺. 79

¹HNMR (300 MHz, CDCl₃): δ 8.61 (d, J = 3.0 Hz, 1H), 7.97- 7 .90 (m, 2H),7.58 (s, 1H), 7.46 (t, J = 3.0 Hz, 6.0 Hz, 1H), 7.37 (d, J = 6.0 Hz,1H), 7.05 (s, 1H), 6.65 (d, J = 9.0 Hz, 1H), 5.88-5.85 (m, 1H), 5.77 (s,2H), 5.22-5.10 (m, 2H), 4.56-4.54 (m, 2H), 2.27 (s, 3H), 2.11 (s, 3H);LC-MS: m/z 388.2 (M + 1)⁺. 80

¹H NMR (400 MHz, DMSO-d₆) δ 8.52 (d, J = 3.9 Hz, 1H), 7.90 (d, J = 9.8Hz, 1H), 7.77-7.75 (m, 1H), 7.61 (s, 1H), 7.31-7.28 (m, 2H), 7.09 (s,1H), 6.59 (d, J = 9.3 Hz, 1H), 5.63 (s, 2H), 4.83 (t, J = 5.3 Hz, 1H),3.96 (t, J = 4.9 Hz, 2H), 3.64-3.60 (m, 2H), 2.27 (s, 3H), 2.10 (s, 3H);ES-MS: m/z 392.2 (M + 1)⁺. 81

¹H NMR (300 MHz, CDCl₃) δ 8.57 (d, J = 4.2 Hz, 1H), 7.67- 7.59 (m, 2H),7.33-7.18 (m, 4H), 6.68 (d, J = 9.6 Hz, 1H), 5.67 (s, 2H), 4.07 (t, J =5.7 Hz, 2H), 2.80 (t, J = 5.4 Hz, 2H), 2.47 (m, 4H), 2.27 (s, 3H), 2.14(s, 3H), 1.74 (m, 4H); LC-MS: m/z 445.2 (M + 1)⁺.  82*

¹H NMR (400 MHz, DMSO-d₆): δ 8.51 (d, J = 4.0 Hz, 1H), 7.90 (d, J = 9.2Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.61 (s, 1H), 7.31-7.28 (m, 2H), 7.10(s, 1H), 6.57 (d, J = 9.6 Hz, 1H), 5.64 (s, 2H), 4.04 (t, J = 5.6 Hz,2H), 2.68-2.64 (m, 5H), 2.61-2.59 (m, 2H), 2.28-2.26 (m, 7H), 2.10 (s,3H); LC-MS: m/z 460.3 (M + 1)⁺. 83

¹H NMR (400 MHz, DMSO-d₆): δ 8.46 (d, J = 5.4 Hz, 2H), 8.41 (d, J = 4.4Hz, 1H), 7.91 (d, J = 9.3 Hz, 1H), 7.71-7.69 (m, 1H), 7.67 (s, 1H),7.26-7.12 (m, 5H), 6.58 (d, J = 9.3 Hz, 1H), 5.57 (s, 2H), 5.22 (s, 2H),2.26 (s, 3H), 2.07 (s, 3H); LC-MS: m/z 439.2 (M + 1)⁺. 84

¹H NMR (400 MHz, DMSO-d₆): δ 8.51 (d, J = 4.4 Hz, 1H), 7.90 (d, J = 9.8Hz, 1H), 7.76 (t, J = 7.8 Hz, 1H), 7.60 (s, 1H), 7.30 (d, J = 7.8 Hz,2H), 7.11 (s, 1H), 6.57 (d, J = 9.3 Hz, 1H), 5.63 (s, 2H), 4.51 (t, J =4.8 Hz, 1H), 4.0 (t, J = 6.4 Hz, 2H), 3.42-3.38 (m, 2H), 2.24 (s, 3H),2.06 (s, 3H), 1.77-1.72 (m, 2H); LC-MS: m/z 406.2 (M + 1)⁺.Note: Synthesis of Compound 77 comprises deprotection reaction accordingto the procedure depicted in below step:

Deprotection Reaction (for Compound-77)6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-onehydrochloride

A solution of tert-butyl4-(((6-(3,5-dimethylisoxazol-4-yl)-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate(0.05 g, 0.0919 mmol) in 1,4-dioxane. HCl (2 mL) was stirred at roomtemperature for 4 h. After completion of reaction, the solvent wasremoved under reduced pressure, residue was triturated with ether andhexane to give the title compound (0.01 g, 22.6%).

Similarly synthesis of Compound 82 comprises deprotection reactionaccording to the procedure depicted herein after.

Deprotection Reaction (for Compound-82)6-(3,5-dimethylisoxazol-4-yl)-7-(2-(piperazin-1-yl)ethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

To a cooled solution of tert-butyl4-(2-((6-(3,5-dimethylisoxazol-4-yl)-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-7-yl)oxy)ethyl)piperazine-1-carboxylate(0.05 g, 0.09 mmol) in DCM (3 mL) was added TFA (0.5 mL) and stirred atroom temperature for 2 h. The reaction mixture concentrated, residue wasdiluted with DCM (50 mL) and washed with sat NaHCO₃ (50 mL), water (50mL), dried over sodium sulphate and concentrated invacuo. The residuewas washed with diethyl ether to afford the title compound as brownsolid (0.015 g, 37%).

Example-X: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(trifluoromethoxy)quinolin-2(1H)-one (Compound-85)

Step-(i): Synthesis of7-(bromodifluoromethoxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

The process of this adopted from step-(ii) of compound-71 (Example-IX)to give the titled compound as pale yellow solid (0.05 g, 36%). ¹H NMR(300 MHz, CDCl₃): δ 8.58 (d, J=4.8 Hz, 1H), 7.74-7.63 (m, 3H), 7.42 (s,1H), 7.29 (d, J=5.1 Hz, 1H), 7.20-7.19 (m, 1H), 6.87 (d, J=9.6 Hz, 1H),5.66 (s, 2H), 2.29 (s, 3H), 2.15 (s, 3H); ¹⁹F NMR (300 MHz, CDCl₃): δ15.9; LC-MS: m/z 477.9 (M+1)⁺.

Step-(ii): Synthesis of6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(trifluoromethoxy)quinolin-2(1H)-one

In a 50 mL polypropylene flask, a stirred solution of7-(bromodifluoromethoxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(0.05 g, 0.105 mmol) in DCM (5 mL) was treated with AgBF₄ (0.061 g,0.315 mmol), at −78° C. for 30 min. The reaction mixture was stirred atRT for 12 h. The reaction mixture was diluted with cold saturated NaHCO₃and extracted with DCM. The organic extract was washed with water andbrine. The organic layer was separated and dried over Na₂SO₄. Thesolution was concentrated under reduced pressure to give crude compound.The residue obtained was purified by silica gel preparative TLC (50%EtOAc/Hexane) to yield the title compound as an off white solid (0.016g, 37%). ¹H NMR (300 MHz, CDCl₃): δ 8.58 (d, J=4.2 Hz, 1H), 7.72-7.61(m, 3H), 7.41 (s, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.23-7.19 (m, 1H), 6.84(d, J=9.6 Hz, 1H), 5.64 (s, 2H), 2.28 (s, 3H), 2.14 (s, 3H); ¹⁹F NMR(300 MHz, CDCl₃): δ −57.95; LC-MS: m/z 416.4 (M+1)⁺.

Example-XI: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-yloxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-onehydrochloride (Compound-86)

Step-(i): Synthesis of tert-butyl4-((6-(3,5-dimethylisoxazol-4-yl)-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-7-yl)oxy)piperidine-1-carboxylate

To a solution of compound-72 (0.07 g, 0.20 mmol) in dry THF (8 mL) wasadded tert-butyl 4-hydroxypiperidine-1-carboxylate (0.05 g, 0.22 mmol),triphenylphosphine (0.16 g, 0.6 mmol), and DIAD (0.12 mL, 0.6 mmol), andstirred at room temperature 16 h. The reaction mixture diluted withwater and extracted with EtOAc (50 mL×2), combined organic layer washedwith brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified by silica gel (60-120 mesh) column chromatography(elution 20-40% EtOAc-hexane) to afford title compound (0.05 g, 47%);LC-MS: m/z 531.3 (M+1)⁺.

Step-(ii): Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-yloxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-onehydrochloride

The process of this adopted from deprotection reaction of compound-77(Example-IX). ¹H NMR (400 MHz, CD₃OD): δ 8.69 (d, J=5.6 Hz, 1H), 8.16(m, 1H), 7.98 (d, J=12.0 Hz, 1H), 7.67-7.65 (m, 2H), 7.57 (d, J=8.0 Hz,1H), 7.26 (s, 1H), 6.66 (d, J=8.0 Hz, 1H), 5.86 (s, 2H), 5.00-4.80 (m,1H), 3.18-3.11 (m, 2H), 3.05-3.01 (m, 2H), 2.29 (s, 3H), 2.13 (s, 3H),2.05-2.03 (m, 2H), 1.84-1.82 (m, 2H); LC-MS: m/z 431.1 (M+1)⁺.

The below compounds were prepared by procedure similar to any or both ofthe steps depicted in Example XI with appropriate variations inreactants, quantities of reagents and reaction conditions. Thephysiochemical characteristics of the compounds are summarized hereinbelow table.

Compound No. Structure Characterization Data 87

¹H NMR (300 MHz, CDCl₃): δ 8.56 (d, J = 4.2 Hz, 1H), 7.66- 7.61 (m, 2H),7.34 (d, J = 7.8 Hz, 1H), 7.23-7.20 (m, 3H), 6.68 (d, J = 9.6 Hz, 1H),5.68 (s, 2H), 3.98-3.93 (m, 2H), 3.76 (d, J = 6.9 Hz, 2H), 3.35 (m, 2H),2.25 (s, 3H), 2.11 (s, 3H), 1.95- 1.91 (m, 1H), 1.39-1.25 (m, 4H);LC-MS: m/z 446.3 (M + 1)⁺. 88

¹H NMR (400 MHz, CDCl₃): δ 8.78 (d, J = 5.6 Hz, 1H), 8.35 (m, 1H), 8.00(d, J = 10 Hz, 1H), 7.85 (m, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.63 (s,1H), 7.15 (s, 1H), 6.64 (d, J = 9.6 Hz, 1H), 5.92 (s, 2H), 4.19-4.14 (m,2H), 2.88 (t, J = 12.8 Hz, 2H), 2.27 (s, 3H), 2.11 (s, 3H), 1.85 (d, J =14 Hz, 2H), 1.71-1.66 (m, 2H), 1.66-1.33 (m, 2H), 1.26 (m, 3H); LC-MS:m/z 459.0 (M + 1)⁺. 89

1H NMR (300 MHz, CD₃OD): 8.82 (d, J = 5.7 Hz, 1H), 8.45- 8.40 (m, 1H),8.03 (d, J = 9.6 Hz, 1H), 7.96-7.90 (m, 1H), 7.76 (d, J = 8.1 Hz, 1H),7.67 (s, 1H), 7.19 (s, 1H), 6.66 (d, J = 9.6 Hz, 1H), 5.99 (s, 2H),4.30-4.20 (m, 2H), 3.80-3.60 (m, 2H), 3.25- 3.10 (m, 1H), 2.75-2.65 (m,1H), 2.40-2.30 (m, 1H), 2.31 (s, 3H), 2.14 (s, 3H), 2.15-2.05 (m, 1H),1.98-1.85 (m, 2H), 1.70-1.55 (m, 1H); LC-MS: m/z 445.2 (M + 1)⁺.

Example-XII: Synthesis of7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-4-((1-propionylpiperidin-4-yl)methyl)-2H-benzo[b][1,4]oxazin-3(4H)-one(Compound-90)

To an ice cooled solution of compound-60 (0.10 g, 0.27 mmol) in DCM (5mL) were added triethyl amine (0.1 mL, 0.8 mmol) followed by addition ofpropionyl chloride (0.04 g, 0.40 mmol) drop wise and stirred at RT for 3h. After completion of reaction, the reaction mixture was diluted withDCM (50 mL) and washed with aq. NaHCO₃ solution (20 mL), water (50 mL),brine (20 mL), dried over sodium sulphate and concentrated. The obtainedresidue was purified by preparative HPLC to afford the title product asan off-white solid (0.08 g, 8%). ¹H NMR (400 MHz, DMSO-d₆): δ 6.92 (s,1H), 6.90 (s, 1H), 4.62 (s, 2H), 4.40-4.32 (m, 1H), 3.90-3.80 (m, 2H),3.80-3.75 (m, 4H), 2.80-2.75 (m, 1H), 2.47-2.40 (m, 5H), 2.20-1.80 (m,5H), 1.72-1.60 (m, 2H), 1.30-1.10 (m, 2H), 0.97 (t, J=7.3 Hz, 3H);LC-MS: m/z 428.3 (M+1)⁺.

Example-XIII: Synthesis of7-methoxy-6-(5-methyl-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(Compound-91)

Step-(i): Synthesis of6-amino-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

In a 100 mL resealable tube, a solution of6-bromo-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one (1.0 g, 2.99mmol) in DMSO (10 mL), was treated sequentially with sodium azide (0.28g, 4.2 mmol), CuI (0.54 g, 2.99 mmol) and L-proline (0.50 g, 4.3 mmol)at RT under a nitrogen atmosphere. The resulting mixture was heatedovernight at 100° C. Upon completion of the reaction (TLC), the reactionmixture was diluted with cold water and extracted with EtOAc (3×50 mL).The combined organic layers were washed with brine and concentratedunder reduced pressure to afford the title compound as pale brown solid(0.60 g, 74%), which was used in the next step without furtherpurification. ¹H NMR (400 MHz, CDCl₃): δ 8.53 (d, J=3.6 Hz, 1H),7.56-7.51 (m, 2H), 7.20-7.13 (m, 2H), 6.95 (s, 1H), 6.77 (s, 1H), 6.62(d, J=8.8 Hz, 1H), 5.64 (s, 2H), 3.8 (s, 3H); LC-MS: m/z 282.1 (M+1)⁺.

Step-(ii): Synthesis of6-isocyanato-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

To a solution of triphosgene (0.35 g, 1.24 mmol) in DCM (2 mL) was addeddrop wise a solution of6-amino-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one (0.35 g, 1.24mmol) in DCM (10 mL) followed by the drop wise addition of triethylamine(0.1 mL, 2.48 mmol)) at RT. The reaction mixture was stirred at RT for 4h. After completion of the reaction (TLC), the solvent was distilled offunder reduced pressure. The residue obtained was used to next stepwithout any purification (0.30 g, crude); LC-MS: m/z 308.1 (M+1)⁺.

Step-(iii): Synthesis of1-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-3-(prop-2-yn-1-yl)urea

To a stirred solution of6-isocyanato-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one (0.3 g,0.97 mmol) in dry THF (10 mL) was added propargyl amine (0.059 g, 0.97mmol) in THF (1 mL) under argon atmosphere at RT. The reaction mixturewas stirred for 12 h at RT. The reaction mixture was diluted with waterand extracted with EtOAc (3×30 mL). The combined organic extract waswashed with brine and concentrated under reduced pressure. The residueobtained was purified by silica gel (60-120 mesh) column chromatographyand eluting with 20% EtOAc/Hexane afforded the title compound as a paleyellow solid (0.32 g, crude). LC-MS: m/z 363.4 (M+1)⁺.

Step-(iv): Synthesis of7-methoxy-6-(5-methyl-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

To a stirred solution of1-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-3-(prop-2-yn-1-yl)urea(0.3 g, 0.82 mmol) in MeOH (15 mL) was added 5 N sodium methoxide inMeOH (0.5 mL) at RT under nitrogen atmosphere. The reaction mixture wasstirred at reflux temperature for 24 h. After completion of thereaction, was cooled to room temperature and solvent was removed underreduced pressure. The residue obtained was purified by silica gelpreparative TLC (5% MeOH/CHCl₃) to give the compound as an off whitesolid (0.01 g, 3.3%). ¹H NMR (400 MHz, CDCl₃): δ 9.79 (s, 1H), 8.51-8.50(d, J=4.8 Hz, 1H), 7.92 (d, J=9.6 Hz, 1H), 7.76-7.74 (m, 1H), 7.63 (s,1H), 7.31-7.26 (m, 2H), 7.11 (s, 1H), 6.58 (d, J=8.4 Hz, 1H), 6.18 (s,1H), 7.74 (d, J=16.8 Hz, 1H), 7.55 (d, 16.8 Hz, 1H), 3.69 (s, 3H), 1.69(3H); LC-MS: m/z 363.0 (M+1)⁺.

Example-XIV: Synthesis of3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione(Compound-92)

Step-(i): Synthesis of1-(3,4-dimethoxybenzyl)-3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione

The process of this step was adopted from example-VII (Compound-17). Thedesired compound obtained as a crude material (0.10 g); LC-MS: m/z 526.1(M+1)⁺.

Step-(ii): Synthesis of3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione

A solution of1-(3,4-dimethoxybenzyl)-3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione(0.10 g, 0.19 mmol), anisole (0.1 mL) and H₂SO₄ (catalytic amount) inTFA (4 mL) was heated over night at 90° C. Upon completion of thereaction (TLC), the reaction mixture was cooled to RT and diluted withDCM. The organic layer was washed with saturated NaHCO₃ solution anddried over anhydrous sodium sulfate, before evaporating under reducedpressure. The obtained residue was purified by silica gel (60-120 mesh)column chromatography and eluting with 5% DCM/MeOH gave the titlecompound as an off-white solid (0.004 g, 5.6%). ¹H NMR (400 MHz, CDCl₃):δ 8.54-8.53 (m, 1H), 7.95-7.90 (m, 1H), 7.77-7.74 (m, 1H), 7.62 (s, 1H),7.34-7.27 (m, 2H), 7.07 (s, 1H), 6.67 (d, J=9.3 Hz, 1H), 5.74 (s, 2H),3.78 (s, 3H), 1.90 (s, 3H); LC-MS: m/z 376.1 (M+1)⁺.

Example-XV: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinoxalin-2(1H)-one (Compound-93)

Step-(i): Synthesis of5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitroaniline

The process of this step was adopted from Example-VII (compound-17). Thedesired compound obtained as a pale yellow solid. ¹HNMR (400 MHz,DMSO-d₆) δ 7.49 (s, 1H), 7.26 (bs, 2H), 6.95 (s, 1H), 3.75 (s, 3H), 2.30(s, 3H), 2.11 (s, 3H); LC-MS: m/e 264.2 (M+1)⁺.

Step-(ii): Synthesis of tert-butyl(5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitrophenyl) carbamate

A stirred suspension of 60% NaH (0.091 g, 2.28 mmol) in 5 mL of DMF at0° C. was added 5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitroaniline(0.5 g, 1.90 mmol). Stirred at same conditions for 30 min then addedBoc-anhydride (0.48 mL, 2.09 mmol). The reaction mixture was stirred for3 h at room temperature. The reaction mixture was diluted with ethylacetate and washed with water (100 mL), dried over Na₂SO₄ andconcentration. The obtained residue was purified by columnchromatography on silica (20% EtOAc in hexane) to give the desiredproduct as a yellow solid (0.45 g, 65%). ¹H NMR (400 MHz, DMSO-d₆) δ9.38 (bs, 1H), 7.61 (s, 1H), 7.41 (s, 1H), 3.85 (s, 3H), 2.30 (s, 3H),2.11 (s, 3H), 1.43 (s, 9H); LC-MS: m/e 364.2 (M+1)⁺.

Step-(iii): Synthesis of tert-butyl(2-amino-5-(3,5-dimethylisoxazol-4-yl)-4-methoxyphenyl) carbamate

A stirred solution of tert-butyl(5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-nitrophenyl) carbamate (0.45g, 1.23 mmol) in 10 mL of MeOH was added 10% Pd—C (0.1 g) and stirredunder H₂ balloon pressure at RT for 2 h. After completion of reaction,the reaction mixture was filtered through celite pad, washed withmethanol. The filtrate was concentrated to afford the title product aspale yellow solid (0.5 g). The crude product was as such taken forwardfor next step without further purification. ¹H NMR (400 MHz, DMSO-d₆) δ8.31 (s, 1H), 6.87 (bs, 1H), 6.44 (s, 1H), 5.01 (bs, 2H), 3.65 (s, 3H),2.21 (s, 3H), 2.03 (s, 3H), 1.43 (s, 9H); LC-MS: m/e 334.2 (M+1)⁺.

Step-(iv): Synthesis of tert-butyl(5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-((pyridin-2-ylmethyl)amino)phenyl)carbamate

To an ice-cooled solution of tert-butyl(2-amino-5-(3,5-dimethylisoxazol-4-yl)-4-methoxyphenyl)carbamate (0.15g, 0.45 mmol) in MeOH (10 mL) were add pyridine-2-carboxaldehyde (0.06mL, 0.67 mmol) and stirred at RT for 2 h. Then the reaction mixture wasagain cooled to 0° C. and added sodium cyanoborohydride (0.057 g, 0.9mmol) followed by AcOH (0.02 mL) and stirred at RT for 16 h. Aftercompletion of reaction, the reaction mixture was concentrated, dilutedwith water and extracted with EtOAc (100 mL×2). The combined organiclayers were washed with aq. sodium bicarbonate (20 mL), water (200 mL),brine (100 mL), dried over sodium sulphate and concentrated. The residuewas purified silica gel (100-200 mesh) to afford the title product (0.1g, 52%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.54 (d, J=4.4 Hz, 1H), 8.31 (s,1H), 7.80-7.76 (m, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.30-7.27 (m, 1H), 6.84(s, 1H), 6.35-6.25 (m, 1H), 5.94 (t, J=5.6 Hz, 1H), 4.47 (d, J=5.4 Hz,2H), 3.61 (s, 3H), 2.20 (s, 3H), 2.02 (s, 3H), 1.23 (s, 9H); LC-MS: m/z425.3 (M+1)⁺.

Step-(v): Synthesis of tert-butyl(2-(2-chloro-N-(pyridin-2-ylmethyl)acetamido)-5-(3,5-dimethylisoxazol-4-yl)-4-methoxyphenyl)carbamate

To an ice-cooled solution of tert-butyl(5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-((pyridin-2-ylmethyl)amino)phenyl)carbamate(0.1 g, 0.23 mmol) in DCM (10 mL) were add NaHCO₃ (0.197 g, 2.35 mmol)followed by 2-chloroacetyl chloride (0.022 g, 0.28 mmol) and stirred at0° C. for 10 min. Reaction mixture was diluted with DCM (100 mL), washedwith water (50 mL), brine (20 mL), dried over sodium sulphate andconcentrated. The residue was as such used for next step without furtherpurification (0.1 g, 85%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.05-10.80 (bs,1H), 8.54 (d, J=4.4 Hz, 1H), 7.89-7.85 (m, 1H), 7.70 (s, 1H), 7.49-7.41(m, 1H), 7.39-7.37 (m, 1H), 7.22 (s, 1H), 4.35-4.20 (m, 4H), 3.75 (s,3H), 2.30 (s, 3H), 2.07 (s, 3H), 1.23 (s, 9H); LC-MS: m/z 502.2 (M+1)⁺.

Step-(vi): Synthesis of tert-butyl7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-oxo-4-(pyridin-2-ylmethyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate

To an ice-cooled solution of tert-butyl(5-(3,5-dimethylisoxazol-4-yl)-4-methoxy-2-((pyridin-2-ylmethyl)amino)phenyl)carbamate(0.1 g, 0.20 mmol) in DMF (5 mL) was add NaH (0.0.12 g, 0.29 mmol) andstirred at 0° C. for 15 min. After completion of reaction, the reactionmixture was quenched with MeOH, diluted with H₂O (10 mL) and extractedwith EtOAc (50 mL×2). The organic layer was washed with water (50 mL),brine (20 mL), dried over sodium sulphate and concentrated. The residuewas as such used for next step without further purification (0.093 g,100%); LC-MS: m/z 465.3 (M+1)⁺.

Step-(vii): Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinoxalin-2(1H)-one

To an ice-cooled solution of tert-butyl7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-oxo-4-(pyridin-2-ylmethyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate(0.1 g, 0.21 mmol) in DCM (5 mL) was add TFA (0.016 mL, 2.15 mmol) andstirred at RT for 3 h. After completion of reaction, the reactionmixture was diluted with DCM (100 mL), washed with aq. sodiumbicarbonate solution (20 mL), water (50 mL), brine (20 mL), dried oversodium sulphate and concentrated. The residue was purified bypreparative TLC to afford the title compound as pale brown solid (0.015g, 19%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.50 (d, J=4.0 Hz, 1H), 8.20 (s,1H), 7.80 (t, J=7.1 Hz, 1H), 7.12 (s, 1H), 7.45 (d, J=7.9 Hz, 1H),7.33-7.29 (m, 1H), 7.13 (s, 1H), 5.64 (s, 2H), 3.77 (s, 3H), 2.26 (s,3H), 2.06 (s, 3H); LC-MS: m/z 363.2 (M+1)⁺.

Example-XVI: Synthesis of N-(4-(4-chlorobenzyl)-6-methoxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3,5-dimethylisoxazole-4-carboxamide(Compound-94)

Step-(i): Synthesis ofN-(4-(4-chlorobenzyl)-6-methoxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3,5-dimethylisoxazole-4-carboxamide

To a solution of7-amino-4-(4-chlorobenzyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(0.10 g, 0.31 mmol) in DCM (5 mL) were added3,5-dimethylisoxazole-4-carboxylic acid (0.05 g, 0.33 mmol), HOBt (0.02,0.15 mmol), EDC.HCl (0.12 g, 0.63 mmol), Triethylamine (0.11 ml, 0.77mmol) and stirred at RT for 16 h. After completion of reaction, thereaction mixture was diluted with DCM (100 mL), washed with water (50mL), brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified by preparative TLC to afford title product as ayellow solid (0.03 g 22%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.08 (bs, 1H),7.63 (s, 1H), 7.40 (d, J=8.3 Hz, 2H), 7.35 (d, J=8.3 Hz, 2H), 6.80 (s,1H), 5.22 (s, 2H), 4.73 (s, 2H), 3.70 (s, 3H), 3.56 (s, 3H), 2.34 (s,3H); LC-MS: m/z 442.1 (M+1)⁺.

Example-XVII: Synthesis of4-(4-chlorobenzyl)-7-((3,5-dimethylisoxazol-4-yl)amino)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(Compound-95)

To a solution of7-bromo-4-(4-chlorobenzyl)-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one(0.10 g, 0.26 mmol) in toluene (5.0 mL) in a sealed tube were added3,5-dimethylisoxazol-4-amine (0.03 g, 0.26 mmol), cesium carbonate (0.20g, 0.65 mmol), xantphos (0.02 g, 0.025 mmol) and degassed with nitrogenpurging for 20 min. Then palladium(II)acetate (0.015 g, 0.065 mmol) wasadded and heated at 100° C. for 16 h. After completion of reaction, thereaction mixture was allowed RT, diluted with EtOAc (50 mL), washed withwater (50 mL), brine (50 mL), dried over sodium sulphate andconcentrated. The residue was purified by preparative TLC to afford thetitle product as pale brown solid (6 mg, 0.5%). ¹H NMR (400 MHz,DMSO-d₆) δ 7.41 (d, J=8.3 Hz, 2H), 7.35 (d, J=8.3 Hz, 2H), 6.66 (s, 1H),6.57 (s, 1H), 5.14 (bs, 2H), 4.59 (s, 2H), 3.70 (s, 3H), 2.18 (s, 3H),1.98 (s, 3H); LC-MS: m/z 414.1 (M+1)⁺.

Example-XVIII: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(Compound-96) &6-(3,5-dimethylisoxazol-4-yl)-3-(fluoromethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(Compound-97)

Step-(i): Synthesis of6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

To an ice cooled solution of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde(0.07 g, 0.18 mmol) in MeOH (3 mL) was added NaBH₄ (0.007 g, 0.18 mmol)pinch wise and stirred at 0° C. for 1 h. After completion of reaction,the reaction mixture concentrated, the residue was diluted with waterand extracted with EtOAc (50 mL×2). The organic layer was washed brine(100 mL), dried over sodium sulphate and concentrated under reducedpressure and column purified to afford the title product as white solid(0.02 g, 28%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.52 (d, J=8.4 Hz, 1H), 7.91(s, 1H), 7.77 (t, J=7.8 Hz, 1H), 7.62 (s, 1H), 7.32-7.28 (m, 2H), 7.11(s, 1H), 5.75 (s, 2H), 5.27 (t, J=5.4 Hz, 1H), 4.46 (d, J=5.4 Hz, 2H),3.73 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z 392.1 (M+1)⁺.

Step-(ii): Synthesis of6-(3,5-dimethylisoxazol-4-yl)-3-(fluoromethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one

To a cooled solution of6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one(0.04 g, 0.102 mmol) in DCM (2 mL) was added DAST (0.04 mL, 0.3 mmol)and stirred at room temperature for 2 h. The reaction mixture dilutedwith DCM (50 mL) and washed with water (50 mL), dried over sodiumsulphate and concentrated under reduced pressure and purified bypreparative TLC to afford the title compound as an off white solid (0.01g, 25%). ¹H NMR (300 MHz, CDCl₃): δ 8.53-8.51 (m, 1H), 7.72 (s, 1H),7.58 (t, J=7.4 Hz, 1H), 7.29 (d, J=7.8 Hz, 1H), 7.24 (s, 1H), 7.16-7.14(m, 2H), 5.64 (bs, 2H), 5.51 (s, 1H), 5.40 (s, 1H), 3.74 (s, 3H), 2.20(s, 3H), 2.06 (s, 3H); LC-MS: m/z 394.2 (M+1)⁺.

Example-XIX: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)quinolin-2(1H)-one(Compound-98)

Step-(i):1-((5-bromopyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one

The process of this adopted from step-d of Intermediate-78.

¹H NMR (400 MHz, DMSO-d₆): δ 8.65 (d, J=2.0 Hz, 1H), 8.03 (dd, J₁=2.4Hz, J₂=8.8 Hz, 1H), 7.91 (d, J=9.3 Hz, 1H), 7.63 (s, 1H), 7.34 (d, J=8.3Hz, 1H), 7.07 (s, 1H), 6.57 (d, J=9.3 Hz, 1H), 5.63 (s, 2H), 3.76 (s,3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z 442 (M+2)²⁺.

Step-(ii):6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)quinolin-2(1H)-one

The process of this was adopted from compound-17 (Example-VII). ¹H NMR(400 MHz, DMSO-d₆): δ 8.77 (d, J=2.0 Hz, 1H), 8.21 (s, 1H), 7.94-7.89(m, 3H), 7.62 (s, 1H), 7.32 (d, J=8.3 Hz, 1H), 7.19 (s, 1H), 6.58 (d,J=9.3 Hz, 1H), 5.63 (s, 2H), 3.86 (s, 3H), 3.77 (s, 3H), 2.24 (s, 3H),2.05 (s, 3H); LC-MS: m/z 442.7 (M+1)⁺.

Example-XX: Synthesis of1-((5-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one(Compound-99)

The process of this was adopted from compound-17 (Example-VII). ¹H NMR(400 MHz, DMSO-d₆): δ 12.39 (bs, 1H), 8.47 (d, J=1.4 Hz, 1H), 7.91 (d,J=9.3 Hz, 1H), 7.14 (dd, J₁=2.4 Hz, J₂=8.3 Hz, 1H), 7.63 (s, 1H), 7.37(d, J=8.3 Hz, 1H), 7.23 (s, 1H), 6.59 (d, J=9.3 Hz, 1H), 5.66 (s, 2H),3.78 (s, 3H), 2.25 (s, 9H), 2.06 (s, 3H); LC-MS: m/z 456.2 (M+1)⁺.

Example-XXI: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-1-((5-(3-hydroxypyrrolidin-1-yl)pyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one(Compound-100)

To a solution of1-((5-bromopyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one(0.05 g, 0.11 mmol) in 1,4-dioxane (4 mL) in a sealed tube were addedpyrrolidin-3-ol (0.01 g, 0.13 mmol), cesium carbonate (0.11 g, 0.34mmol) and BINAP (0.004 g, 0.006 mmol) and degassed with nitrogen purgingfor 15 min then added palladium acetate (0.003 g, 0.011 mmol), thenheated at 100° C. for 16 h. After completion of the reaction, thereaction mixture was diluted with EtOAc (50 mL), washed with water (50mL), brine (50 mL), dried over sodium sulphate and concentrated. Theresidue was purified by preparative TLC to afford the title compound asbrown solid (0.02 g, 43%). ¹H NMR (400 MHz, DMSO-d₆): δ 7.91 (d, J=9.8Hz, 1H), 7.85 (s, 1H), 7.60 (s, 1H), 7.30 (s, 1H), 7.20 (d, J=8.8 Hz,1H), 6.99-6.97 (m, 1H), 6.59 (d, J=9.3 Hz, 1H), 5.53 (bs, 2H), 4.41-4.39(m, 1H), 3.82 (s, 3H), 3.60-3.30 (m, 4H), 3.10 (d, J=10.3 Hz, 1H), 2.24(s, 3H), 2.06 (s, 3H), 2.03-1.91 (m, 2H); LC-MS: m/z 447.1 (M+1)⁺.

Example-XXII: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(Compound-101)

To a cooled solution of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinoline-3-carbaldehyde(0.02 g, 0.051 mmol) in THF (1 mL) were added tetra butyl ammoniumfluoride 1.0 M in THF (0.015 mL, 0.015 mmol) and TMS-CF₃ (0.01 mL, 0.061mmol), stirred at 0° C. for 1 h. The reaction mixture quenched with sat.NH₄Cl, extracted with EtOAc (50 mL), washed with water (50 mL), driedover sodium sulphate and concentrated. The residue was purified onpreparative TLC to afford the title compound as an off white solid (0.01g, 43%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.52 (d, J=3.9 Hz, 1H), 8.19 (s,1H), 7.80-7.77 (m, 2H), 7.33-7.28 (m, 2H), 7.15 (s, 1H), 6.90 (d, J=7.4Hz, 1H), 5.77-5.64 (m, 2H), 5.49-5.43 (m, 1H), 3.76 (s, 3H), 2.25 (s,3H), 2.07 (s, 3H); LC-MS: m/z 460.2 (M+1)⁺.

The above compound-101 (racemate) was purified by chiral HPLC. Thecharacterization data of desired isomers was given below.

Compound No. Structure Characterization Data 102 & 103

Compound 102 (Isomer-1): ¹H NMR (400 MHz, DMSO-d₆): δ 8.52 (d, J = 4.4Hz, 1H), 8.18 (s, 1H), 7.80 (s, 1H), 7.79-7.77 (m, 1H), 7.33-7.29 (m,2H), 7.15 (s, 1H), 6.90 (d, J = 6.0 Hz, 1H), 5.77-5.64 (m, 2H),5.49-5.44 (m, 1H), 3.76 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS: m/z460.1 (M + 1)⁺. Compound 103 (Isomer-2): ¹H NMR (400 MHz, DMSO-d₆): δ8.52 (d, J = 4.4 Hz, 1H), 8.19 (s, 1H), 7.80 (s, 1H), 7.79-7.77 (m, 1H),7.33-7.29 (m, 2H) 7.15 (s, 1H), 6.90 (d, J = 5.6 Hz, 1H), 5.77-5.64 (m,2H), 5.48-5.45 (m, 1H), 3.76 (s, 3H), 2.25 (s, 3H), 2.06 (s, 3H); LC-MS:m/z 460.1 (M + 1)⁺.

Example-XXIII: Synthesis of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1,1-dihydroxyethyl)quinolin-2(1H)-one(Compound-104)

To cooled solution of6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(0.2 g, 0.43 mmol) in DCM (5 mL) was added dess-martin per iodinane(0.28 g, 0.65 mmol) and stirred at room temperature for 16 h. Aftercompletion of the reaction, the reaction mixture was diluted with DCM(100 mL) and washed with mixture of aqueous NaHCO₃ and Na₂S₂O₅ in 5:1ratio dried over sodium sulphate and concentrated. The residue waspurified by preparative HPLC to afford title compound as white solid(0.015 g, 8%). ¹H NMR (400 MHz, DMSO-d₆): δ 8.55 (s, 2H), 8.50 (d, J=4.9Hz, 1H), 8.40 (s, 1H), 7.94 (s, 1H), 7.82 (t, J=6.9 Hz, 1H), 7.39 (d,J=7.8 Hz, 1H), 7.32-7.29 (m, 1H), 7.23 (s, 1H), 5.77 (s, 2H), 3.79 (s,3H), 2.26 (s, 3H), 2.07 (s, 3H); ES-MS: m/z 476.1 (M+1)⁺.

Example-XXIV: Synthesis of1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-2-oxo-1,2-dihydroquinoline-4-carbonitrile(Compound-105) &2-(1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)acetonitrile:(Compound-106)

Step-(i): Synthesis of6-bromo-1-(4-chlorophenethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde

The process of this was adopted from step-(i) of compound-1 (Example-I).¹H NMR (400 MHz, CDCl₃): δ 10.42 (s, 1H), 8.24 (s, 1H), 7.89 (s, 1H),7.30 (d, J=8.3 Hz, 2H), 7.20 (d, J=8.3 Hz, 2H), 6.63 (s, 1H), 4.48 (t,J=7.8 Hz, 2H), 3.96 (s, 3H), 3.06 (t, J=7.8 Hz, 2H); LC-MS: m/z 421.0(M+1)⁺.

Step-(ii): Synthesis of1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde

The process of this was adopted from compound-17 (Example-VII). ¹H NMR(400 MHz, CDCl₃): δ 10.45 (s, 1H), 8.33 (s, 1H), 7.46 (s, 1H), 7.30 (d,J=8.3 Hz, 2H), 7.22 (d, J=8.3 Hz, 2H), 6.67 (s, 1H), 4.53 (t, J=7.9 Hz,2H), 3.89 (s, 3H), 3.10 (t, J=7.8 Hz, 2H), 2.31 (s, 3H), 2.15 (s, 3H);LC-MS: m/z 437.1 (M+1)⁺.

Step-(iii): Synthesis of1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxyquinolin-2(1H)-one

The process of this was adopted from compound-97 (Example-XVIII-). Thedesired compound obtained as a white solid (0.2 g, 67%). ¹H NMR (400MHz, CDCl₃): δ 7.64 (s, 1H), 7.32-7.21 (m, 5H), 6.67 (s, 1H), 4.66-4.64(m, 2H), 4.52 (t, J=7.8 Hz, 2H), 3.86 (s, 3H), 3.35-3.30 (m, 1H), 3.08(t, J=7.8 Hz, 2H), 2.31 (s, 3H), 2.16 (s, 3H); LC-MS: m/z 439.1 (M+1)⁺.

Step-(iv): Synthesis of1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)methylmethanesulfonate

The process of this step was adopted from intermediate-15. The obtainedcrude was used in the next step without any purification.

Step-(v): Synthesis of1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-2-oxo-1,2-dihydroquinoline-4-carbonitrile&2-(1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)acetonitrile

To a cooled solution of(1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)methylmethanesulfonate(0.22 g, 0.43 mmol) in DMF (5 mL) was added potassium cyanide (0.042 g,0.64 mmol) and stirred at room temperature for 16 h. After completion ofthe reaction, the reaction mixture poured into ice water and extractedwith EtOAc (100×2), dried over sodium sulphate, concentrated underreduced pressure and column purified to afford title compound as paleyellow solid (A) (0.02 g, 10%). ¹H NMR (400 MHz, CDCl₃): δ 7.64 (s, 1H),7.30 (d, J=8.3 Hz, 2H), 7.21 (d, J=8.3 Hz, 2H), 6.73 (s, 1H), 4.51 (t,J=7.4 Hz, 2H), 3.86 (s, 3H), 3.07 (t, J=7.8 Hz, 2H), 2.53 (s, 3H), 2.33(s, 3H), 2.17 (s, 3H); LC-MS: m/z 448.1 (M+1)⁺. & (B) (0.065 g, 34%). ¹HNMR (400 MHz, CDCl₃): δ 7.89 (s, 1H), 7.37 (s, 1H), 7.30-7.28 (m, 2H),7.21 (d, J=8.8 Hz, 2H), 6.72 (s, 1H), 4.52 (t, J=7.3 Hz, 2H), 3.87 (s,3H), 3.75 (d, J=1.5 Hz, 2H), 3.07 (t, J=7.9 Hz, 2H), 2.32 (s, 3H), 2.17(s, 3H); LC-MS: m/z 448.1 (M+1)⁺.

BIOLOGICAL DATA

In-Vitro Biochemical Data of bicyclic heterocyclic derivatives intime-resolved fluorescence resonance energy transfer (TR-FRET) assay.

The Bet bromodomain TR-FRET assay has been used to identify compoundsthat bind to bet bromodomain and prevent its interaction with acetylatedhistone peptides.

In the assay, optimized concentration of in-house Bet bromodomainprotein (BRD4) and 300 nM of acetyl histone peptide substrate werediluted in assay buffer (50 mM HEPES, pH: 7.5, 50 mM NaCl, 500 μM CHAPS)and were added to the positive control and test control wells in a 384well plate. Substrate control wells have 300 nM of acetyl histonepeptide substrate diluted in assay buffer. Buffer blank wells were addedwith assay buffer. The reaction mixture was allowed for incubation atroom temperature for 30 mins. Stock solutions of test compounds at 20 mMDMSO are prepared. Compounds are serially diluted and added to the testwells in 384-well polypropylene plates. The reaction mixture was furtherincubated for 30 mins at room temperature on a plate shaker. 2 nM ofEuropium labeled streptavidn and 10 nM of XL-665 labeled antibodydiluted in detection buffer (50 mM HEPES, pH: 7.5, 50 mM NaCl, 500 μMCHAPS and 800 mM KF) were added to all the wells excluding the bufferblank wells. The reaction plate was incubated for additional 30 mins atroom temperature on plate shaker. The plate was read in Perkin ElmerWALLAC 1420 Multilabel Counter Victor 3 (Ex: 340 nm Em: 615 and 665 nm).The amount of displacement of the peptide was measured as ratio ofspecific 665 nm energy transfer signal to 615 nm signals. The compoundsIC₅₀ was determined by fitting the dose response data to sigmoid curvefitting equation using Graph Pad Prism software V5.

The compounds were screened in the above mentioned assay and the results(IC₅₀) are summarized in the table below; wherein “A” refers to an IC₅₀value of less than or equal to 1000 nM, “B” refers to IC₅₀ value inrange of 1000.01 to 3000 nM and “C” refers to IC₅₀ value of greater than3000 nM.

Group Compound No A 1, 2, 4, 5, 7, 8, 9, 10, 16, 17, 18, 20, 21, 22, 23,24, 26, 28, 29, 32, 34, 36, 37, 38, 39, 40, 41, 43, 44, 45, 46, 47, 49,50, 55, 56, 58, 59, 62, 64, 65, 66, 67, 68, 69, 72, 73, 74, 77, 78, 79,80, 83, 84, 89, 90, 93, 96, 97, 98, 101, 102, 103, 104, 106. B 11, 12,25, 27, 30, 31, 33, 35, 42, 51, 53, 57, 75, 81, 82, 85, 87, 88. C 3, 6,13, 14, 15, 19, 48, 52, 54, 60, 61, 63, 70, 71, 76, 86, 91, 92, 94, 95,105.

We claim:
 1. A compound of formula (I):

or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof; wherein, dotted line represents a single bond or adouble bond; X is selected from C or C(O); wherein C is substituted withone or more R₅ to meet the desired valency requirements; L₁ is a directbond or a linker selected from —NH—, —NHC(O)—, or —NHS(O)₂—; L₂ is alinker selected from —(CHR₆)_(n)—, —C(O)—, or —S(O)₂; Cy₁ is anoptionally substituted 5-6 membered monocyclic ring containing 1-4hetero atoms/hetero groups independently selected from N, NH, O, or—C(O)—; wherein the optional substituent at each occurrence isindependently selected from one or more R₇; Cy₂ is an optionallysubstituted 4-12 membered monocyclic or bicyclic ring containing 0-3hetero atoms/hetero groups independently selected from N, NH, O, or S;wherein the optional substituent at each occurrence is independentlyselected from one or more R₈; R₁ is selected from hydrogen, alkyl,alkenyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, heterocyclyl,or heterocyclylalkyl; R₂ and R₃ independently are hydrogen, alkyl, ortogether form an oxo group; R₄ at each occurrence is independentlyselected from hydrogen, alkyl, cycloalkyl, cyanoalkyl, hydroxyalkyl, oroptionally substituted haloalkyl; wherein the optional substituent isone or more hydroxyl; R₅ at each occurrence is independently selectedfrom hydrogen, alkyl, haloalkyl, cycloalkyl, or cyano; R₆ is hydrogen oralkyl; R₇ is selected from alkyl, hydroxyl, or cycloalkyl; R₈ isselected from alkyl, alkoxy, amino, cyano, halogen, haloalkyl, hydroxy,—C(O)alkyl, or optionally substituted heterocyclyl; wherein the optionalsubstituent is selected from one or more alkyl or hydroxy; and n is aninteger selected from 1 or
 2. 2. The compound according to claim 1,wherein X is CH.
 3. The compound according to claim 1, wherein Cy₁ is3,5-dimethylisoxazole.
 4. The compound according to claim 1, wherein L₁is a direct bond.
 5. The compound according to claim 1, wherein L₂ is—CH₂—.
 6. The compound according to claim 1, wherein Cy₂ is optionallysubstituted pyridyl or optionally substituted phenyl.
 7. The compoundaccording to claim 6, wherein the optional substituent is halogen,haloalkyl, alkoxy, amino, or cyano.
 8. The compound according to claim1, wherein R₄ is alkyl, cyanoalkyl, hydroxyalkyl, or optionallysubstituted haloalkyl; wherein the optional substituent is hydroxy. 9.The compound according to claim 1, wherein the compound is a compound offormula (Ib):

wherein, the dotted line, R₁, R₂, R₃, R₄, Cy₁, Cy₂, L₁, L₂, and n arethe same as defined in claim 1; or a pharmaceutically acceptable salt ora pharmaceutically acceptable stereoisomer thereof.
 10. A compoundselected from the group consisting of:6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-methoxypyridin-2-yl)methyl)quinolin-2(1H)-one;6-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrazin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-((3-fluoropyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one;1-((4-chlorophenyl)sulfonyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;1-(4-chlorobenzoyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2(1H)-one;1-((5-chloropyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(2-morpholinoethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(thiazol-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(1-(pyridin-2-yl)ethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(1-(pyridin-3-yl)ethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(2-(pyridin-2-yl)ethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrimidin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyrimidin-4-ylmethyl)quinolin-2(1H)-one;6(3,5-dimethylisoxazol-4-yl)-1-((5-fluoropyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(trifluoromethyl)pyridin-2-yl)methyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-4,4-dimethyl-1-(pyridin-2-ylmethyl)-3,4-dimethylisoxazol-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridin-2-ylmethyl)quinoline-2,4(1H,3H)-dione;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridine-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-4-methyl-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-4-(trifluoromethyl)quinolin-2(1H)-one;4-cyclopropyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;1-(4-chlorobenzyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(quinolin-2-ylmethyl)quinolin-2(1H)-one;1-((5-chloropyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methylquinolin-2(1H)-one;1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methylquinolin-2(1H)-one;6-(6-hydroxypyridin-3-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3-cyclopropyl-5-methylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;7-methoxy-6-(5-methylisoxazol-4-yl)-1-(pyridine-2-ylmethyl)quinolin-2(1H)-one;7-methoxy-6-(3-methylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethyl-1H-pyrazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;1-((6-chloropyridin-3-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;3-cyclohexyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;3-cyclohexyl-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-hydroxy-1-(pyridin-2-ylmethyl)quinolin-2(1H-one;1-((5-chloropyridin-2yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-hydroxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2,2,2-trifluoroethoxy)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(2-morpholinoethoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;7-(2-(dimethylamino)ethoxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;7-butoxy-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;7-(allyloxy)-6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(2-hydroxyethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(2-(piperazin-1-yl)ethyl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(pyridin-4-ylmethoxy)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(3-hydroxypropoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(trifluoromethoxy)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(piperidin-4-yloxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-((tetrahydro-2H-pyran-4-yl)methoxy)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-(2-(piperidin-4-yl)ethoxy)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(pyrrolin-3-yl)ethoxy)quinolin-2(1H)-one;7-methoxy-6-(5-methyl-2-oxo-2,3-dihydro-1H-imidazo-1-yl)-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;3-(7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydroquinolin-6-yl)-4-methyl-1H-pyrrole-2,5-dione;6-(3,5-dimethylisoxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-3-(fluoromethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)quinolin-2(1H)-one;1-((5-bromopyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;1-((5-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-1-((5-(3-hydroxypyrrolidin-1-yl)pyridin-2-yl)methyl)-7-methoxyquinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2(1H)-one;6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(Isomer-1);6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2(1H)-one(Isomer-2);6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1,1-dihydroxyethyl)quinolin-2(1H)-one;1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-3-methyl-2-oxo-1,2-dihydroquinoline-4-carbonitrile;and2-(1-(4-chlorophenethyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)acetonitrile,or a pharmaceutically acceptable salt or a pharmaceutically acceptablestereoisomer thereof.
 11. A pharmaceutical composition comprising atherapeutically effective amount of at least one compound of formula (I)according to claim 1, or a pharmaceutically acceptable salt or apharmaceutically acceptable stereoisomer thereof and at least onepharmaceutically acceptable carrier or excipient including mixturesthereof in all ratios.